Drug Information

Drug (ID: DG00151) and It's Reported Resistant Information

• Name: Paclitaxel
• Synonyms: C47H51NO14; weekly paclitaxel; Micellar Paclitaxel; Paclitaxel [USAN:INN:BAN]; SCHEMBL15000506; Benzenepropanoic acid, beta-(benzoylamino)-alpha-hydroxy-, 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca(3,4)benz(1,2-b)oxet-9-yl ester, (2aR-(2aalpha,4beta,4abeta,6beta,9alpha(alphaR*,betaS*),11alpha,12alpha,12aalpha,12balpha))-
• Indication:
  In total 5 Indication(s)
  Breast cancer [ICD-11: 2C60]; Approved; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Approved; [1]
  Pancreatic cancer [ICD-11: 2C10]; Phase 3; [1]
  Ovarian cancer [ICD-11: 2C73]; Phase 2; [1]
  Stomach cancer [ICD-11: 2B72]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (6 diseases)
  Brain cancer [ICD-11: 2A00]; [2]
  Breast cancer [ICD-11: 2C60]; [3]
  Cervical cancer [ICD-11: 2C77]; [4]
  Head and neck cancer [ICD-11: 2D42]; [5]
  Ovarian cancer [ICD-11: 2C73]; [7]
  Prostate cancer [ICD-11: 2C82]; [8]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Lung cancer [ICD-11: 2C25]; [6]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (20 diseases)
  Bladder cancer [ICD-11: 2C94]; [9]
  Breast cancer [ICD-11: 2C60]; [10]
  Cervical cancer [ICD-11: 2C77]; [11]
  Colorectal cancer [ICD-11: 2B91]; [12]
  Endometrial cancer [ICD-11: 2C76]; [13]
  Epithelial ovarian cancer [ICD-11: 2B5D]; [14]
  Esophageal cancer [ICD-11: 2B70]; [15]
  Gastric cancer [ICD-11: 2B72]; [16]
  Liver cancer [ICD-11: 2C12]; [10]
  Lung cancer [ICD-11: 2C25]; [17]
  Melanoma [ICD-11: 2C30]; [18]
  Nasopharyngeal cancer [ICD-11: 2B6B]; [19]
  Osteosarcoma [ICD-11: 2B51]; [20]
  Ovarian cancer [ICD-11: 2C73]; [21]
  Pancreatic cancer [ICD-11: 2C10]; [22]
  Pleural mesothelioma [ICD-11: 2C26]; [23]
  Prostate cancer [ICD-11: 2C82]; [17]
  Skin squamous cell carcinoma [ICD-11: 2C31]; [10]
  Testicular cancer [ICD-11: 2C80]; [24]
  Uterine sarcoma [ICD-11: 2C72]; [17]
• Target: Apoptosis regulator Bcl-2 (BCL-2); BCL2_HUMAN; [1]
• Target: Tubulin beta (TUBB); NOUNIPROTAC; [1]
• Formula: C47H51NO14
• IsoSMILES: CC1=C2[C@H](C(=O)[C@@]3([C@H](C[C@@H]4[C@]([C@H]3[C@@H]([C@@](C2(C)C)(C[C@@H]1OC(=O)[C@@H]([C@H](C5=CC=CC=C5)NC(=O)C6=CC=CC=C6)O)O)OC(=O)C7=CC=CC=C7)(CO4)OC(=O)C)O)C)OC(=O)C
• InChI: 1S/C47H51NO14/c1-25-31(60-43(56)36(52)35(28-16-10-7-11-17-28)48-41(54)29-18-12-8-13-19-29)23-47(57)40(61-42(55)30-20-14-9-15-21-30)38-45(6,32(51)22-33-46(38,24-58-33)62-27(3)50)39(53)37(59-26(2)49)34(25)44(47,4)5/h7-21,31-33,35-38,40,51-52,57H,22-24H2,1-6H3,(H,48,54)/t31-,32-,33+,35-,36+,37+,38-,40-,45+,46-,47+/m0/s1
• InChIKey: RCINICONZNJXQF-MZXODVADSA-N
• PubChem CID: 36314
• ChEBI ID: CHEBI:45863
• TTD Drug ID: D0C4RB
• VARIDT ID: DR00342
• INTEDE ID: DR1227
• DrugBank ID: DB01229

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Epidermal growth factor receptor (EGFR) [25]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Non-small cell lung cancer
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.41E-78; Fold-change: -3.81E-01; Z-score: -2.43E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: 95D cells; Lung; Homo sapiens (Human); CVCL_7110
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Overexpression of miR-7 sensitizes NSCLC cells to PTX and inhibites EGFR expression in A549 cells.

Key Molecule: Procathepsin L (CTSL) [30]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.73E-08; Fold-change: 1.55E-01; Z-score: 5.62E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: A miRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial-mesenchymal transition.

Key Molecule: Signal transducer activator transcription 3 (STAT3) [56]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.92E-04; Fold-change: -1.90E-02; Z-score: -3.57E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H1155 cells; Lung; Homo sapiens (Human); CVCL_1456
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Over-expression of miR-337-3p nor the specific knockdown of STAT3 and RAP1A significantly decrease cell viability or induce G2/M arrest alone, but rather enhance G2/M arrest and cell death only under conditions of paclitaxel treatment.

Key Molecule: Microtubule-associated protein tau (MAPT) [59]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.52E-04; Fold-change: -2.94E-02; Z-score: -3.44E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: p53 signaling pathway; Activation; hsa04115
• In Vitro Model: Calu3 cells; Lung; Homo sapiens (Human); CVCL_0609
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: H4006 cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: 293FT cells; Kidney; Homo sapiens (Human); CVCL_6911
• In Vitro Model: HCC95 cells; Lung; Homo sapiens (Human); CVCL_5137
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Luciferase assay
• Experiment for Drug Resistance: CellTiter-Glo assay
• Mechanism Description: miR186 regulates chemo-sensitivity to paclitaxel via targeting MAPT in non-small cell lung cancer The chemosensitizing effects of miR186 are partially due to the induction of the p53 mediated apoptotic pathway via MAPT down-regulation.

Key Molecule: Procathepsin L (CTSL) [30]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.16E-12; Fold-change: -4.59E-02; Z-score: -7.43E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: A miRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial-mesenchymal transition.

Key Molecule: Transcriptional coactivator YAP1 (YAP1) [61]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.93E-18; Fold-change: -5.64E-02; Z-score: -9.07E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H441 cells; Lung; Homo sapiens (Human); CVCL_1561
• In Vitro Model: H2172 cells; Lung; Homo sapiens (Human); CVCL_1537
• In Vitro Model: H827 cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: PC-14 cells; Lung; Homo sapiens (Human); CVCL_1640
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Wound-healing and Transwell assay
• Mechanism Description: miR-424-3p was discovered to suppress the level of YAP1 protein by targeting its 3' untranslated region, suggesting that miR-424-3p could be a potential molecular target for treatment of NSCLC with chemoresistance.

Key Molecule: G1/S-specific cyclin-D1 (CCND1) [64]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.49E-14; Fold-change: -8.39E-02; Z-score: -7.82E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT/mTOR signaling pathway; Regulation; N.A.
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: NCl-H596 cells; Lung; Homo sapiens (Human); CVCL_1571
• In Vitro Model: NCI-H1734 cells; Lung; Homo sapiens (Human); CVCL_1491
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-16 was also significantly downregulated in paclitaxel resistant lung cancer cells. anti-apoptotic protein Bcl-2 was directly targeted miR-16 in paclitaxel resistant lung cancer cells. the combined overexpression of miR-16 and miR-17 and subsequent paclitaxel treatment greatly sensitized paclitaxel resistant lung cancer cells to paclitaxel by inducing apoptosis via caspase-3 mediated pathway. Combined overexpression of miR-16 and miR-17 greatly reduced Beclin-1 and Bcl-2 expressions respectively. though miR-17 and miR-16 had no common target, both miR-16 and miR-17 jointly played roles in the development of paclitaxel resistance in lung cancer. miR-17 overexpression reduced cytoprotective autophagy by targeting Beclin-1, whereas overexpression of miR-16 potentiated paclitaxel induced apoptotic cell death by inhibiting anti-apoptotic protein Bcl-2.

Key Molecule: Bcl-2-like protein 2 (BCL2L2) [68]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.83E-48; Fold-change: -1.29E-01; Z-score: -1.85E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Dual-luciferase reporter assay; qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis; Caspase-3 activity assay
• Mechanism Description: Overexpression of miR107 promotes apoptosis and inhibits proliferation and mobility of A549/Taxol cells under treatment with paclitaxel in vitro. miR107/Bcl-w axis regulates paclitaxel chemoresistance through PI3k-Akt pathway, up-regulation of miR107 resensitizes paclitaxel-resistant NSCLC cells by targeting Bcl-w. Aberrant activation of PI3k-Akt pathway and genetic alterations of its components lead to tumorigenesis.

Key Molecule: Mucin-1 (MUC1) [71]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.28E-51; Fold-change: -1.53E-01; Z-score: -1.59E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• Cell Pathway Regulation: Rapamycin signaling pathway; Inhibition; hsa04211
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Luciferase activity assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR128 can effectively suppress PTX-resistant lung cancer stem cells via inhibition of BMI-1 and MUC1-C, thus downregulating the PI3k/AkT pathway and the rapamycin pathway.

Key Molecule: Ras-related protein Rap-1A (RAP1A) [56]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.74E-117; Fold-change: -1.82E-01; Z-score: -3.62E+01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H1155 cells; Lung; Homo sapiens (Human); CVCL_1456
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Over-expression of miR-337-3p nor the specific knockdown of STAT3 and RAP1A significantly decrease cell viability or induce G2/M arrest alone, but rather enhance G2/M arrest and cell death only under conditions of paclitaxel treatment.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: CX3C chemokine receptor 1 (CX3CR1) [74]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.74E-47; Fold-change: -2.56E-01; Z-score: -1.79E+01
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: Calu3 cells; Lung; Homo sapiens (Human); CVCL_0609
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: SPC-A1 cells; Lung; Homo sapiens (Human); CVCL_6955
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: NCI-H358 cells; Lung; Homo sapiens (Human); CVCL_1559
• In Vitro Model: H157 cells; Lung; Homo sapiens (Human); CVCL_2458
• In Vitro Model: D6 cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: LAX cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: LTEP-2 cells; Lung; Homo sapiens (Human); CVCL_6929
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR296-3p inhibited NSCLC cell proliferation, enhance the drug resistance, and apoptosis. Data of luciferase reporter assays demonstrated that the CX3CR1 gene was a direct regulator of tumorsuppressive miR296-3p. Moreover, overexpressed CX3CR1 was confirmed in NSCLC clinical specimens. Inhibition of CX3CR1 could inhibit cancer cellular survival and increase chemotherapy sensitivity. There was a negative relationship between miR296-3p and CX3CR1 expression in NSCLC tissues.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Nuclear paraspeckle assembly transcript 1 (NEAT1) [75]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.10E-61; Fold-change: -1.67E+00; Z-score: -1.91E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: H1573 cells; Lung; Homo sapiens (Human); CVCL_1478
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: NEAT1 was upregulated significantly in paclitaxel-resistant NSCLC cell line while knockdown of NEAT1 could reverse the paclitaxel-resistance through induction of apoptosis by increasing cleaved PARP and cleaved caspase-3 expression.

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Hypoxia-inducible factor 1-alpha inhibitor (HIF1AN) [17]

• Resistant Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Non-small cell lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 9.37E-05; Fold-change: -1.00E-01; Z-score: -3.99E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Hypoxia-inducible factor 1-alpha inhibitor (HIF1AN) is a protein that binds to HIF-1alpha and inhibits its transcriptional activity. HIF1AN is a potential miR-135a target listed in both the TargetScan and PicTar databases. miR-135a-mediated paclitaxel resistance is in part mediated by downregulation of APC.

Key Molecule: RAC serine/threonine-protein kinase (AKT) [35]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.32E-02; Fold-change: -5.24E-02; Z-score: -2.29E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: 16HBE cells; Lung; Homo sapiens (Human); CVCL_0112
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Overexpression of HOTTIP promotes proliferation and drug resistance of lung adenocarcinoma by regulating AkT signaling pathway.

Key Molecule: Catenin delta-1 (CTNND1) [36]

• Resistant Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Non-small cell lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.34E-02; Fold-change: -5.18E-02; Z-score: -1.80E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: SPC-A1 cells; Lung; Homo sapiens (Human); CVCL_6955
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; CCK8 assay; Colony formation assay; Flow cytometry assay
• Mechanism Description: MALAT1 could alter chemo-resistance (Cisplatin, Adriamycin, Gefitinib and Paclitaxel) of NSCLC cells by targeting miR-197-3p and regulating p120-ctn expression, which might assist in improvement of chemo-therapies for NSCLC.

Key Molecule: Beclin-1 (BECN1) [42]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.69E-15; Fold-change: 3.96E-02; Z-score: 8.38E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Trypan blue exclusion assay; Flow cytometry assay
• Mechanism Description: Overexpression of miR-17-5p sensitized paclitaxel resistant lung cancer cells to paclitaxel induced apoptotic cell death. miR-17-5p directly binds to the 3'-UTR of beclin 1 gene, one of the most important autophagy modulator. Overexpression of miR-17-5p into paclitaxel resistant lung cancer cells reduced beclin1 expression and a concordant decease in cellular autophagy. Paclitaxel resistance of lung cancer is associated with downregulation of miR-17-5p expression which might cause upregulation of BECN1 expression.

Key Molecule: Poly[ADP-ribose] synthase 1 (PARP1) [38]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.62E-122; Fold-change: 1.35E-01; Z-score: 3.17E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/Taxol cells; Lung; Homo sapiens (Human); CVCL_W218
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell Invasion assay
• Mechanism Description: ANRIL, also known as CDkN2B antisense RNA1, was origi.lly identified in the familial melanoma patients, it is located within the CDkN2B-CDkN2A gene cluster at chromosome 9p21. ANRIL decreases Bcl-2 expression and increases PARP expression.

Key Molecule: Transcriptional activator protein Pur-alpha (PURA) [20]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.38E-11; Fold-change: -6.39E-02; Z-score: -6.98E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Silencing of MA-linc1 in unsynchronized cells results in fewer cells in G1 and a concomitant increase in the number of cells in all other stages of the cell cycle, particularly in G2/M. Moreover, its silencing in M phase-arrested cells inhibits mitosis exit. The effect of MA-linc1 on cell cycle progression is mediated, at least in part, by repression of its neighboring gene, Puralpha, a cell cycle regulator whose expression induces cell cycle arrest. Importantly, high levels of MA-linc1 are correlated with decreased survival of breast and lung cancer patients and its silencing sensitizes cancer cells to the apoptotic effect of the M phase specific chemotherapeutic drug, Paclitaxel. This enhancement of Paclitaxel-induced apoptosis is also Puralpha-related.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: CDKN2B antisense RNA 1 (CDKN2B-AS1) [38]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.86E-05; Fold-change: 7.84E-01; Z-score: 4.01E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/Taxol cells; Lung; Homo sapiens (Human); CVCL_W218
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell Invasion assay
• Mechanism Description: ANRIL, also known as CDkN2B antisense RNA1, was origi.lly identified in the familial melanoma patients, it is located within the CDkN2B-CDkN2A gene cluster at chromosome 9p21. ANRIL decreases Bcl-2 expression and increases PARP expression.

Key Molecule: HOXA distal transcript antisense RNA (HOTTIP) [35]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.34E-04; Fold-change: 3.02E+00; Z-score: 3.68E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: 16HBE cells; Lung; Homo sapiens (Human); CVCL_0112
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Overexpression of HOTTIP promotes proliferation and drug resistance of lung adenocarcinoma by regulating AkT signaling pathway.

Key Molecule: Mitosis associated long intergenic non-coding RNA 1 (MALINC1) [20]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.58E-01; Fold-change: 2.06E-01; Z-score: 1.41E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Silencing of MA-linc1 in unsynchronized cells results in fewer cells in G1 and a concomitant increase in the number of cells in all other stages of the cell cycle, particularly in G2/M. Moreover, its silencing in M phase-arrested cells inhibits mitosis exit. The effect of MA-linc1 on cell cycle progression is mediated, at least in part, by repression of its neighboring gene, Puralpha, a cell cycle regulator whose expression induces cell cycle arrest. Importantly, high levels of MA-linc1 are correlated with decreased survival of breast and lung cancer patients and its silencing sensitizes cancer cells to the apoptotic effect of the M phase specific chemotherapeutic drug, Paclitaxel. This enhancement of Paclitaxel-induced apoptosis is also Puralpha-related.

Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) [36]

• Resistant Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: SPC-A1 cells; Lung; Homo sapiens (Human); CVCL_6955
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; CCK8 assay; Colony formation assay; Flow cytometry assay
• Mechanism Description: MALAT1 could alter chemo-resistance (Cisplatin, Adriamycin, Gefitinib and Paclitaxel) of NSCLC cells by targeting miR-197-3p and regulating p120-ctn expression, which might assist in improvement of chemo-therapies for NSCLC.

Key Molecule: hsa-miR-197-3p [36]

• Resistant Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: SPC-A1 cells; Lung; Homo sapiens (Human); CVCL_6955
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; CCK8 assay; Colony formation assay; Flow cytometry assay
• Mechanism Description: MALAT1 could alter chemo-resistance (Cisplatin, Adriamycin, Gefitinib and Paclitaxel) of NSCLC cells by targeting miR-197-3p and regulating p120-ctn expression, which might assist in improvement of chemo-therapies for NSCLC.

Key Molecule: CDKN2B antisense RNA 1 (CDKN2B-AS1) [38]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/Taxol cells; Lung; Homo sapiens (Human); CVCL_W218
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell Invasion assay
• Mechanism Description: ANRIL functioning as a potential oncogene was up-regulated in LAD, and promoted the acquisition of chemo-resistance in paclitaxel partly through the mitochondrial pathway by modulating the expression of apoptosis-related protein cleaved-PARP and Bcl-2. ANRIL decreases Bcl-2 expression and increases PARP expression.

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aldo-keto reductase family 1 member B10 (AKR1B10) [6]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: MU375/MU383 patient-derived tumor organoids; Homo sapiens
• Experiment for Molecule Alteration: qPCR; IHC assay
• Experiment for Drug Resistance: Drug sensitivity testing
• Mechanism Description: Epalrestat can be repurposed to overcome chemoresistance. PDTOs retained histomorphology and pathological biomarker expression, mutational/transcriptomic signatures, and cellular heterogeneity of the matched tumor tissues. Five (50%) PDTOs were chemoresistant toward carboplatin/paclitaxel. Chemoresistant PDTOs and matched tumor tissues demonstrated overexpression of AKR1B10. Epalrestat, an orally available AKR1B10 inhibitor in clinical use for diabetic polyneuropathy, was repurposed to overcome chemoresistance of PDTOs. In vivo efficacy of epalrestat to overcome drug resistance corresponded to intratumoral epalrestat levels.

Ovarian cancer [ICD-11: 2C73]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Glutathione S-transferase P (GSTP1) [26]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.41E-06; Fold-change: 3.22E-01; Z-score: 4.97E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The upregulation of GST-Pi cause excessive intensity of detoxification of cytostatics, affect drug metabolism and influence the effects of chemotherapy, which results in resistance for paclitaxel in the ovarian cancer cells.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Tubulin beta-3 chain (TUBB3) [37]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.94E-02; Fold-change: 8.18E-02; Z-score: 2.01E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vitro Model: MES-OV cells; Ovary; Homo sapiens (Human); CVCL_CZ92
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: SRB colorimetric assay; Flow cytometry assay
• Mechanism Description: The miR-200 family has major roles in EMT and taxane resistance in taxane selected ovarian cancer cell variants, and that re-introduction of miR-200s was not sufficient to fully reverse the mesenchymal phenotype in these variants. Although miR-200s were able to restore paclitaxel sensitivity in one of the variants, they did not do so in the other, and produced resistance to carboplatin in both. The divergent effects of miR-200s on taxane and carboplatin cytotoxicity should be further investigated in ovarian cancers. miR-200c and miR-141 mimics conferred resistance to carboplatin in MES-OV/TP cells, similar to OVCAR-3/TP, but sensitized MES-OV to paclitaxel. Several genes involved in balancing oxidative stress were altered in OVCAR-3/TP 200c141 cells compared to controls. The miR-200 family plays major, cell-context dependent roles in regulating EMT and sensitivity to carboplatin and paclitaxel in OVCAR-3 and MES-OV cells.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: E3 ubiquitin-protein ligase Mdm2 (MDM2) [46]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.89E-01; Fold-change: 2.25E-02; Z-score: 9.05E-01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: Hey A8 cells; Ovary; Homo sapiens (Human); CVCL_8878
• In Vitro Model: SkVO3ip1 cells; Ovary; Homo sapiens (Human); CVCL_0C84
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Down-regulation of miR-194-5p induces paclitaxel resistance in ovarian cancer cells by altering MDM2 expression.

Key Molecule: CUB domain-containing protein 1 (CDCP1) [1]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.85E-05; Fold-change: 1.92E-01; Z-score: 7.30E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: MYC/WNT/AKT signaling pathway; Regulation; N.A.
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vivo Model: NMRI-nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Time course proliferation assay; Flow cytometry assay
• Mechanism Description: CDCP1 and PLAGL2 oncogenes were found to be the most relevant direct miR-654-5p targets and both genes convey in a molecular signature associated with key cancer pathways relevant to ovarian tumorigenesis, such as MYC, WNT and AkT pathways.

Key Molecule: Zinc finger protein PLAGL2 (PLAGL2) [1]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.68E-03; Fold-change: 1.41E-01; Z-score: 3.84E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: MYC/WNT/AKT signaling pathway; Regulation; N.A.
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vivo Model: NMRI-nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Time course proliferation assay; Flow cytometry assay
• Mechanism Description: CDCP1 and PLAGL2 oncogenes were found to be the most relevant direct miR-654-5p targets and both genes convey in a molecular signature associated with key cancer pathways relevant to ovarian tumorigenesis, such as MYC, WNT and AkT pathways.

Key Molecule: Myeloid differentiation primary response protein MyD88 (MYD88) [49]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 9.74E-04; Fold-change: 1.06E-01; Z-score: 4.97E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: TLR/MyD88 signaling pathway; Regulation; N.A.
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Transwell assay
• Mechanism Description: In the present study, flow cytometric assays were used to detect the apoptosis of A2780 cells after down-regulation of miRNA-149. We found that down-regulation of miRNA-149 decreased the apoptosis induced by paclitaxel when compared to the control group. Furthermore, we showed that down-regulation of miRNA-149 in A2780 cells (+) the expression of the anti-apoptotic protein Bcl-2 and inhibited the expression of the pro-apoptotic protein bax, which may have led to paclitaxel resistance.

Key Molecule: Growth protein 5 inhibitor (ING5) [58]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.54E-01; Fold-change: -2.41E-02; Z-score: -9.83E-01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780/Taxol cells; Ovary; Homo sapiens (Human); CVCL_IJ13
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Colony formation assay; Apoptosis analysis by FITC immunofluorescence
• Mechanism Description: miR1307 promotes ovarian cancer cell chemoresistance by targeting the ING5 expression.

Key Molecule: Hypoxia-inducible factor 1-alpha inhibitor (HIF1AN) [17]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.45E-01; Fold-change: -2.62E-02; Z-score: -1.00E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Hypoxia-inducible factor 1-alpha inhibitor (HIF1AN) is a protein that binds to HIF-1alpha and inhibits its transcriptional activity. HIF1AN is a potential miR-135a target listed in both the TargetScan and PicTar databases. miR-135a-mediated paclitaxel resistance is in part mediated by downregulation of APC.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Neurogenic locus notch homolog protein 3 (NOTCH3) [28]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.90E-11; Fold-change: -2.73E-01; Z-score: -7.13E+00
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: WST assay; Spheroid formation assay; Colony-forming assay; TUNEL assay; Wound healing assay
• Mechanism Description: microRNA-136 inhibits cancer stem cell activity and enhances the anti-tumor effect of paclitaxel against chemoresistant ovarian cancer cells by targeting Notch3.

Key Molecule: Apoptotic protease-activating factor 1 (APAF1) [47]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.27E-01; Fold-change: 2.19E-02; Z-score: 8.36E-01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Wound healing assay; Invasion assay; CCK8 assay; Flow cytometry assay
• Mechanism Description: miR-630 inhibitor attenuated chemoresistant epithelial ovarian cancer proliferation and invasion, probably by targeting APAF-1, re-sensitizing the cells to chemotherapy.

Key Molecule: Superoxide dismutase Mn (SODM) [66]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Ovarian tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.62E-01; Fold-change: -1.14E-01; Z-score: -1.54E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR146a/SOD2/ROS signaling pathway; Regulation; N.A.
• In Vitro Model: HEY cells; Ovary; Homo sapiens (Human); CVCL_0297
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vitro Model: CAOV3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; TUNEL Assay
• Mechanism Description: miR146a downregulates the expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and enhanced sensitivity to chemotherapy.

Cervical cancer [ICD-11: 2C77]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cadherin-1 (CDH1) [27]

• Resistant Disease: Cervical cancer [ICD-11: 2C77.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Cervical cancer [ICD-11: 2C77]
• The Specified Disease: Cervical cancer
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.15E-02; Fold-change: -8.66E-02; Z-score: -2.06E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: Siha cells; Cervix uteri; Homo sapiens (Human); CVCL_0032
• In Vitro Model: Caski cells; Uterus; Homo sapiens (Human); CVCL_1100
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Paclitaxel transiently induced up-regulation of miR-375 expression, proliferation inhibition, transition from epithelial to mesenchymal phenotype, and consequently impaired paclitaxel sensitivity. Forced over-expression of miR-375 may suppress Ecadherin expression by a directly targeting pathway, which led to paclitaxel resistance. Contrarily, re-expression of Ecadherin partly reversed epithelial-mesenchymal transition phenotype and miR-375 induced paclitaxel-resistance. Our findings suggest that paclitaxel-induced miR-375 over-expression facilitates epithelial-mesenchymal transition process via directly targeting Ecadherin, proliferation inhibition, and consequently results in chemo-resistance in cervical cancer cells.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Pvt1 oncogene (PVT1) [11]

• Resistant Disease: Cervical cancer [ICD-11: 2C77.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Cervical cancer [ICD-11: 2C77]
• The Specified Disease: Cervical & endocervical cancer
• The Studied Tissue: Cervix Uteri
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.35E-02; Fold-change: 6.14E-01; Z-score: 1.84E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Inhibition; hsa01521
• In Vitro Model: Siha cells; Cervix uteri; Homo sapiens (Human); CVCL_0032
• In Vitro Model: Caski cells; Uterus; Homo sapiens (Human); CVCL_1100
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Flow cytometric analysis; CCK8 assay
• Mechanism Description: LncRNA PVT1 epigenetically silences miR195 and modulates EMT and chemoresistance in cervical cancer cells. PVT1 could decrease miR195 expression via enhancing histone H3k27me3 in the miR195 promoter region and also via direct sponging of miR195.

Kidney cancer [ICD-11: 2C90]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Metalloproteinase inhibitor 3 (TIMP3) [29]

• Sensitive Disease: Renal carcinoma [ICD-11: 2C90.2]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Renal carcinoma
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.59E-02; Fold-change: 2.68E+00; Z-score: 3.16E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• In Vitro Model: HK-2 cells; Kidney; Homo sapiens (Human); CVCL_0302
• In Vitro Model: RCC10 cells; Kidney; Homo sapiens (Human); CVCL_6265
• In Vitro Model: RCC4 cells; Kidney; Homo sapiens (Human); CVCL_0498
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
• Mechanism Description: Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.

Key Molecule: Programmed cell death protein 4 (PDCD4) [29]

• Sensitive Disease: Renal carcinoma [ICD-11: 2C90.2]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Renal carcinoma
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.62E-01; Fold-change: 6.66E-03; Z-score: 1.74E-01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• In Vitro Model: HK-2 cells; Kidney; Homo sapiens (Human); CVCL_0302
• In Vitro Model: RCC10 cells; Kidney; Homo sapiens (Human); CVCL_6265
• In Vitro Model: RCC4 cells; Kidney; Homo sapiens (Human); CVCL_0498
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
• Mechanism Description: Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.

Key Molecule: Phosphatase and tensin homolog (PTEN) [29]

• Sensitive Disease: Renal carcinoma [ICD-11: 2C90.2]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Kidney cancer [ICD-11: 2C90]
• The Specified Disease: Renal cancer
• The Studied Tissue: Kidney
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.24E-05; Fold-change: 1.07E-01; Z-score: 6.36E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• In Vitro Model: HK-2 cells; Kidney; Homo sapiens (Human); CVCL_0302
• In Vitro Model: RCC10 cells; Kidney; Homo sapiens (Human); CVCL_6265
• In Vitro Model: RCC4 cells; Kidney; Homo sapiens (Human); CVCL_0498
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
• Mechanism Description: Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.

Endometrial cancer [ICD-11: 2C76]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Zinc finger E-box-binding homeobox 2 (ZEB2) [31]

• Sensitive Disease: Endometrial cancer [ICD-11: 2C76.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Endometrial cancer [ICD-11: 2C76]
• The Specified Disease: Endometrial cancer
• The Studied Tissue: Uterus
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.99E-35; Fold-change: -9.00E-01; Z-score: -1.66E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: Hec50 cells; Endometrium; Homo sapiens (Human); CVCL_2929
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: ELISA assay
• Mechanism Description: Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.

Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1) [31]

• Sensitive Disease: Endometrial cancer [ICD-11: 2C76.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Endometrial cancer [ICD-11: 2C76]
• The Specified Disease: Endometrial cancer
• The Studied Tissue: Uterus
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.45E-43; Fold-change: -1.36E+00; Z-score: -1.98E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: Hec50 cells; Endometrium; Homo sapiens (Human); CVCL_2929
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: ELISA assay
• Mechanism Description: Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.

Key Molecule: Protein quaking (QKI) [31]

• Sensitive Disease: Endometrial cancer [ICD-11: 2C76.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Endometrial cancer [ICD-11: 2C76]
• The Specified Disease: Endometrial cancer
• The Studied Tissue: Uterus
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.05E-34; Fold-change: -6.23E-01; Z-score: -1.68E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: Hec50 cells; Endometrium; Homo sapiens (Human); CVCL_2929
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: ELISA assay
• Mechanism Description: Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibronectin (FN1) [31]

• Sensitive Disease: Endometrial cancer [ICD-11: 2C76.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Endometrial cancer [ICD-11: 2C76]
• The Specified Disease: Endometrial cancer
• The Studied Tissue: Uterus
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.90E-04; Fold-change: -3.04E-01; Z-score: -3.40E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: Hec50 cells; Endometrium; Homo sapiens (Human); CVCL_2929
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: ELISA assay
• Mechanism Description: Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA 672 (LINC00672) [13]

• Resistant Disease: Endometrial cancer [ICD-11: 2C76.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Endometrial cancer [ICD-11: 2C76]
• The Specified Disease: Uterine corpus endometrioid carcinoma
• The Studied Tissue: Endometrium
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.77E-05; Fold-change: -2.11E+00; Z-score: -5.23E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ishikawa cells; Endometrium; Homo sapiens (Human); CVCL_2529
• In Vitro Model: HEC-1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Transwell migration assay; Matrigel invasion assay; Flow cytometry assay; TUNEL assay; Wound healing assay; Colony formation assay
• Mechanism Description: LINC00672 can down-regulate LASP1 expression as a locus-restricted cofactor for p53-mediated gene suppression, thus impacting EC malig.ncies and chemosensitivity to paclitaxel.

Colon cancer [ICD-11: 2B90]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: RAC-beta serine/threonine-protein kinase (AKT2) [32]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Colon cancer [ICD-11: 2B90]
• The Specified Disease: Colon cancer
• The Studied Tissue: Colon tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.42E-11; Fold-change: -2.49E-01; Z-score: -7.11E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The tumor suppressive role of miR-203 was mediated by negatively regulating Akt2 protein expression through mRNA degradation. The inhibition of Akt2 activity downregulated the protein expression of its downstream molecules involved in chemoresistance, such as MTDH and HSP90 genes.

Key Molecule: Aldehyde dehydrogenase 6 (ALDH6) [33]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Colon cancer [ICD-11: 2B90]
• The Specified Disease: Colon cancer
• The Studied Tissue: Colon tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.80E-23; Fold-change: -5.37E-01; Z-score: -1.21E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vivo Model: BALB/C nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR-125a/b significantly inhibited ALDH1A3 and Mcl1 expression, reduced cell survival, and increased cell apoptosis in HT29-taxol cells. Chemoresistance to paclitaxel is initiated by the downregulation of miR-125a/b expression, which subsequently upregulates ALDH1A3 and Mcl1 expression to promote survival of CSCs.

Key Molecule: Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) [33]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Colon cancer [ICD-11: 2B90]
• The Specified Disease: Colon cancer
• The Studied Tissue: Colon tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.73E-07; Fold-change: -7.16E-02; Z-score: -5.12E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vivo Model: BALB/C nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR-125a/b significantly inhibited ALDH1A3 and Mcl1 expression, reduced cell survival, and increased cell apoptosis in HT29-taxol cells. Chemoresistance to paclitaxel is initiated by the downregulation of miR-125a/b expression, which subsequently upregulates ALDH1A3 and Mcl1 expression to promote survival of CSCs.

Key Molecule: Phosphatase and tensin homolog (PTEN) [89]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• Experiment for Molecule Alteration: Northern blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR-22 enhanced the anticancer effect of paclitaxel in the p53-mutated cells through increasing cell apoptosis and reducing cell proliferation and survival. The anticancer role of miR-22 was mediated by activation of PTEN signaling, subsequent inhibition of Akt Ser473 phosphorylation and MTDH expression, as well as upregulation of Bax and active caspase-3 levels.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-125a [33]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vivo Model: BALB/C nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR-125a/b significantly inhibited ALDH1A3 and Mcl1 expression, reduced cell survival, and increased cell apoptosis in HT29-taxol cells. Chemoresistance to paclitaxel is initiated by the downregulation of miR-125a/b expression, which subsequently upregulates ALDH1A3 and Mcl1 expression to promote survival of CSCs.

Key Molecule: hsa-mir-125b [33]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vivo Model: BALB/C nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR-125a/b significantly inhibited ALDH1A3 and Mcl1 expression, reduced cell survival, and increased cell apoptosis in HT29-taxol cells. Chemoresistance to paclitaxel is initiated by the downregulation of miR-125a/b expression, which subsequently upregulates ALDH1A3 and Mcl1 expression to promote survival of CSCs.

Key Molecule: hsa-mir-22 [89]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• Experiment for Molecule Alteration: Northern blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR-22 enhanced the anticancer effect of paclitaxel in the p53-mutated cells through increasing cell apoptosis and reducing cell proliferation and survival. The anticancer role of miR-22 was mediated by activation of PTEN signaling, subsequent inhibition of Akt Ser473 phosphorylation and MTDH expression, as well as upregulation of Bax and active caspase-3 levels.

Key Molecule: hsa-mir-203 [32]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• Experiment for Molecule Alteration: RT-PCR; Northern blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: the tumor suppressive role of miR-203 was mediated by negatively regulating Akt2 protein expression through mRNA degradation. The inhibition of Akt2 activity downregulated the protein expression of its downstream molecules involved in chemoresistance, such as MTDH and HSP90 genes.

Liver cancer [ICD-11: 2C12]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [34]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Hepatocellular carcinoma
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.18E-05; Fold-change: -3.05E-01; Z-score: -4.26E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: Skhep1 cells; Liver; Homo sapiens (Human); CVCL_0525
• In Vitro Model: HCC3 cells; Liver; Homo sapiens (Human); CVCL_0C57
• In Vitro Model: LM-6 cells; Liver; Homo sapiens (Human); CVCL_7680
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: miR-223 targeted ABCB1 3'UTR directly, and miR-223 down-regulated ABCB1 at both mRNA and protein levels. The over-expression of miR-223 increased the HCC cellsensitivity to anticancer drugs, and the inhibition of miR-223 had the opposite effect. Importantly, the over-expression or silencingof ABCB1 can rescue the cell response to the anticancer drugs mediated by miR-223 over-expression or inhibition.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-379 [93]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: IGF1/IGF1R signaling pathway; Inhibition; hsa05200
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Propidium Iodide (PI) Staining
• Mechanism Description: IGF1 is a hub gene in HCC and is involved in the p53 signaling pathway regulation. miR379 can sensitize HCC cells to chemotherapeutic reagents via targeting IGF1R and suppressing its expression, and suppressing the IGF1/IGF1R signaling pathway.

Key Molecule: hsa-mir-335 [94]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: miR335/SIAH2/HDAC3 signaling pathway; Regulation; N.A.
• In Vitro Model: SNU387 cells; Liver; Homo sapiens (Human); CVCL_0250
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Trypan blue exclusion assay; Transwell assay
• Mechanism Description: miR-335-mediated increased sensitivity to anti-cancer drugs was associated with its effect on HDAC3 and SIAH2 expression. miR-335 exerted apoptotic effects and inhibited ubiquitination of HDAC3 in anti-cancer drug-resistant cancer cell lines. miR-335 negatively regulated the invasion, migration, and growth rate of cancer cells. The mouse xenograft model showed that miR-335 negatively regulated the tumorigenic potential of cancer cells. The down-regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The results of the study indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs.

Key Molecule: hsa-mir-223 [34]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: Skhep1 cells; Liver; Homo sapiens (Human); CVCL_0525
• In Vitro Model: HCC3 cells; Liver; Homo sapiens (Human); CVCL_0C57
• In Vitro Model: LM-6 cells; Liver; Homo sapiens (Human); CVCL_7680
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: miR-223 targeted ABCB1 3'UTR directly, and miR-223 down-regulated ABCB1 at both mRNA and protein levels. The over-expression of miR-223 increased the HCC cellsensitivity to anticancer drugs, and the inhibition of miR-223 had the opposite effect. Importantly, the over-expression or silencingof ABCB1 can rescue the cell response to the anticancer drugs mediated by miR-223 over-expression or inhibition.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Insulin-like growth factor 1 receptor (IGF1R) [93]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: IGF1/IGF1R signaling pathway; Inhibition; hsa05200
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Dual luciferase assay; Western blot analysis
• Experiment for Drug Resistance: Propidium Iodide (PI) Staining
• Mechanism Description: IGF1 is a hub gene in HCC and is involved in the p53 signaling pathway regulation. miR379 can sensitize HCC cells to chemotherapeutic reagents via targeting IGF1R and suppressing its expression, and suppressing the IGF1/IGF1R signaling pathway.

Key Molecule: E3 ubiquitin-protein ligase SIAH2 (SIAH2) [94]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: miR335/SIAH2/HDAC3 signaling pathway; Regulation; N.A.
• In Vitro Model: SNU387 cells; Liver; Homo sapiens (Human); CVCL_0250
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Trypan blue exclusion assay; Transwell assay
• Mechanism Description: miR-335-mediated increased sensitivity to anti-cancer drugs was associated with its effect on HDAC3 and SIAH2 expression. miR-335 exerted apoptotic effects and inhibited ubiquitination of HDAC3 in anti-cancer drug-resistant cancer cell lines. miR-335 negatively regulated the invasion, migration, and growth rate of cancer cells. The mouse xenograft model showed that miR-335 negatively regulated the tumorigenic potential of cancer cells. The down-regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The results of the study indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs.

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: I-kappa-B-kinase beta (IKKB) [41]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Liver cancer
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.19E-03; Fold-change: 4.24E-02; Z-score: 3.17E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: NF-kappaB signaling pathway; Activation; hsa04064
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: HCCLM3 cells; Liver; Homo sapiens (Human); CVCL_6832
• In Vitro Model: BEL-7404 cells; Liver; Homo sapiens (Human); CVCL_6568
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: PLC cells; Liver; Homo sapiens (Human); CVCL_0485
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Silencing the expression of miR-16 induced the chemoresistance in HCC by target IkBkB via NF-kB signaling pathway.

Key Molecule: Caspase-3 (CASP3) [10]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Caspase-3 is the key executioner caspase in apoptosis. Ectopic expression of let-7adecreased the luciferase activity of a reporter constructcontaining the 30untranslated region of caspase-3. Enforced let-7aexpression increased the resistance in A431 cells andHepG2 cells to apoptosis induced by therapeutic drugs suchas interferon-gamma, doxorubicin and paclitaxel.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-16 [41]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: NF-kappaB signaling pathway; Activation; hsa04064
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: HCCLM3 cells; Liver; Homo sapiens (Human); CVCL_6832
• In Vitro Model: BEL-7404 cells; Liver; Homo sapiens (Human); CVCL_6568
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: PLC cells; Liver; Homo sapiens (Human); CVCL_0485
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Silencing the expression of miR-16 induced the chemoresistance in HCC by target IkBkB via NF-kB signaling pathway.

Key Molecule: hsa-let-7a [10]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Caspase-3 is the key executioner caspase in apoptosis. Ectopic expression of let-7adecreased the luciferase activity of a reporter constructcontaining the 30untranslated region of caspase-3. Enforced let-7aexpression increased the resistance in A431 cells andHepG2 cells to apoptosis induced by therapeutic drugs suchas interferon-gamma, doxorubicin and paclitaxel.

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Nuclear receptor coactivator 3 (NCOA3) [39]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.70E-17; Fold-change: 5.02E-02; Z-score: 8.64E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MCF-7/Tax1 cells; Breast; Homo sapiens (Human); CVCL_IJ26
• In Vitro Model: MCF-7/Tax2 cells; Breast; Homo sapiens (Human); CVCL_IJ26
• In Vitro Model: MDA-MB-231/Tax1 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-231/Tax2 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR; Western blot analysis; Dual-luciferase activity assay
• Experiment for Drug Resistance: MTT assay; Annexin-V-FITC (fluorescein isothiocyanate)/PI (propidium iodide) analysis
• Mechanism Description: Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3.

Key Molecule: Tumor protein D52 (TPD52) [44]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.37E-86; Fold-change: 2.99E-01; Z-score: 2.53E+01
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Activation; hsa04310
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-107 could enhance PTX sensitivity in breast cancer cells may be targeting TPD52 through Wnt/beta-catenin signaling pathway. And downregualtion of miR-107 ould enhance PTX resistance in BC cells.

Key Molecule: Transcription factor SOX-2 (SOX2) [45]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.42E-05; Fold-change: 2.55E-02; Z-score: 4.37E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Down-regulation of miR 200c 3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2.

Key Molecule: Histone acetyltransferase p300 (EP300) [50]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 9.37E-01; Fold-change: -5.95E-04; Z-score: -7.94E-02
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR106b~25 cluster/EP300/E-cadherin signaling pathway; Regulation; N.A.
• In Vitro Model: MTMECs cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-106b~25 cluster controls transporter-independent MDR by apoptosis evasion via downregulation of EP300.

Key Molecule: Leucine zipper putative tumor suppressor 1 (LZTS1) [54]

• Resistant Disease: Triple negative breast cancer [ICD-11: 2C60.9]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.40E-02; Fold-change: -9.85E-03; Z-score: -1.79E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-1207-5p induces the resistence of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression.

Key Molecule: Endoribonuclease Dicer (DICER1) [55]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.17E-02; Fold-change: -1.56E-02; Z-score: -2.16E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-18a is an important miRNA that suppresses Dicer expression and increases paclitaxel resistance in triple-negative breast cancer cells.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [62]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.08E-24; Fold-change: -5.64E-02; Z-score: -1.09E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• In Vitro Model: MDA-MB-435 cells; Breast; Homo sapiens (Human); CVCL_0417
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Celltiter 96 aqueous one solution cell proliferation assay
• Mechanism Description: miR-125b was up-regulated in Taxol-resistant cells, causing a marked inhibition of Taxol-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to Taxol in cancer cells. The pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) is a direct target of miR-125b. Down-regulation of Bak1 suppressed Taxol-induced apoptosis and led to an increased resistance to Taxol.

Key Molecule: Death-associated protein kinase 2 (DAPK2) [65]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.52E-41; Fold-change: -1.09E-01; Z-score: -1.52E+01
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: Hs-578T cells; Breast; Homo sapiens (Human); CVCL_0332
• In Vitro Model: HBL-100 cells; Breast; Homo sapiens (Human); CVCL_4362
• In Vitro Model: BT483 cells; Breast; Homo sapiens (Human); CVCL_2319
• In Vitro Model: MDA-MB-361 cells; Breast; Homo sapiens (Human); CVCL_0620
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Flow cytometry assay
• Mechanism Description: Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPk2) expression, as restoring DAPk2 abolished miR-520h-promoted drug resistance, and knockdown of DAPk2 mitigated cell death caused by the depletion of miR-520h.

Key Molecule: Transcriptional activator protein Pur-alpha (PURA) [20]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.31E-48; Fold-change: -1.11E-01; Z-score: -1.68E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Silencing of MA-linc1 in unsynchronized cells results in fewer cells in G1 and a concomitant increase in the number of cells in all other stages of the cell cycle, particularly in G2/M. Moreover, its silencing in M phase-arrested cells inhibits mitosis exit. The effect of MA-linc1 on cell cycle progression is mediated, at least in part, by repression of its neighboring gene, Puralpha, a cell cycle regulator whose expression induces cell cycle arrest. Importantly, high levels of MA-linc1 are correlated with decreased survival of breast and lung cancer patients and its silencing sensitizes cancer cells to the apoptotic effect of the M phase specific chemotherapeutic drug, Paclitaxel. This enhancement of Paclitaxel-induced apoptosis is also Puralpha-related.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase mTOR (mTOR) [40]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.52E-01; Fold-change: 4.68E-03; Z-score: 1.44E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: Hs-578T cells; Breast; Homo sapiens (Human); CVCL_0332
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-100 expression was significantly downregulated in breast cancer, and the downregulation was more extensive in luminal A breast cancers and was associated with worse patient survival. Ectopic expression of miR-100 sensitized, while inhibition of miR-100 expression desensitized, breast cancer cells to the effect of paclitaxel on cell cycle arrest, multinucleation, apoptosis and tumorigenesis. Expression of genes that are part of a known signature of paclitaxel sensitivity in breast cancer significantly correlated with miR-100 expression. Mechanistically, targeting mTOR appeared to mediate miR-100's function in sensitizing breast cancer cells to paclitaxel, but other mechanisms also seem to be involved, including targeting other molecules such as PLk1.

Key Molecule: Cyclin-dependent kinase 6 (CDK6) [52]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.73E-01; Fold-change: -7.96E-03; Z-score: -1.36E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LINC00511 positively regulated CDk6 expression in breast cancer cells. And LINC00511 knockdown enhanced paclitaxel cytotoxicity in breast cancer cells by upregulating miR-29c.

Key Molecule: Short transient receptor potential channel 5 (TRPC5) [53]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.61E-02; Fold-change: -9.79E-03; Z-score: -2.42E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: TRPC5 signaling pathway; Regulation; N.A.
• In Vitro Model: MCF-7/ADM cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-320a, which downregulated TRPC5 and NFATC3, colud inreduce chemoresistance.

Key Molecule: E3 ubiquitin-protein ligase CBL-B (CBLB) [57]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.81E-02; Fold-change: -2.30E-02; Z-score: -2.37E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: MAPK/ERK signaling pathway; Inhibition; hsa04010
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: BCap37 cells; Breast; Homo sapiens (Human); CVCL_0164
• In Vitro Model: Bads-200 cells; Breast; Homo sapiens (Human); N.A.
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-27b inhibits proliferation and resistance to PTX of breast cancer cell by repressing CBLB and GRB2 and suppresses activities of PI3k/AkT and MAPk/ERk signaling pathways through downregulation of CBLB and GRB2.

Key Molecule: Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) [67]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.86E-37; Fold-change: -1.22E-01; Z-score: -1.41E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Wnt2/Beta-catenin signaling pathway; Inhibition; hsa04310
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: KPL-4 cells; Breast; Homo sapiens (Human); CVCL_5310
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RIP assay; ChIP assay; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay
• Mechanism Description: Long non-coding RNA LINC00968 attenuates drug resistance of breast cancer cells through inhibiting the Wnt2/beta-catenin signaling pathway by regulating WNT2.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC-type oligopeptide transporter ABCB9 (ABCB9) [51]

• Sensitive Disease: Breast carcinoma [ICD-11: 2C60.2]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.24E-01; Fold-change: -3.94E-03; Z-score: -6.38E-01
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Luciferase assay; Western blot analysis
• Experiment for Drug Resistance: MTT assay; TUNEL assay
• Mechanism Description: Overexpression of microRNA-24 increases the sensitivity to paclitaxel in drug-resistant breast carcinoma cell lines via targeting ABCB9.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Insulin receptor substrate 1 (IRS1) [70]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.48E-38; Fold-change: -1.39E-01; Z-score: -1.40E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/ERK signaling pathway; Inhibition; hsa04010
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Dual-luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay; Wound healing assay; Flow cytometry assay; Caspase-3 Activity Assay
• Mechanism Description: miR30e inhibits tumor growth and chemoresistance via targeting IRS1 in Breast Cancer, by targeting IRS1, miR30e is able to inhibit AkT and ERk1/2 pathways.

Prostate cancer [ICD-11: 2C82]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein kinase Yes (YES1) [8]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Prostate cancer [ICD-11: 2C82]
• The Specified Disease: Prostate cancer
• The Studied Tissue: Prostate
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.64E-01; Fold-change: 3.34E-03; Z-score: 1.72E-01
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PC3/TXR cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: MTT assay; Annexin V-FITC and PI Flow cytometry assay
• Mechanism Description: Overexpression of miR199a inhibited PTX resistance. YES1 was a target of miR199a, and overexpression of YES1 reversed the effect of miR199a in suppressing PTX resistance. In vivo, miR199a increased tumor PTX sensitivity.

Key Molecule: SLAIN motif-containing protein 1 (SLAIN1) [43]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Prostate cancer [ICD-11: 2C82]
• The Specified Disease: Prostate cancer
• The Studied Tissue: Prostate
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.28E-04; Fold-change: 3.25E-01; Z-score: 4.11E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Caspase-3 signaling pathway; Activation; hsa04210
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CellTiter-Glo luminescent cell viability assay
• Mechanism Description: Restoration of miR-130a activated caspase-8 and increased the drug sensitivity in taxane-resistant prostate cancer cells, suggesting that miR-130a may become a potential target for therapy of taxane-resistant CRPC. Since the mechanism of the action of miR-130a was different from that of paclitaxel, a combination therapy of paclitaxel and miR-130a mimic may be effective in treatment of CRPC. Furthermore, it was reported that miR-130a expression was decreased in prostate cancer tissues. It is therefore possible that the restoration of miR-130a could be an effective approach for treating not only taxane-resistant prostate cancer but also prostate cancer with reduced expression of miR-130a.

Key Molecule: Transcription factor GATA6 (GATA6) [48]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Prostate cancer [ICD-11: 2C82]
• The Specified Disease: Prostate cancer
• The Studied Tissue: Prostate
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.12E-02; Fold-change: 1.34E-01; Z-score: 2.48E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: RWPE-1 cells; Prostate; Homo sapiens (Human); CVCL_3791
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Long non-coding RNA Linc00518 Can enhance GATA6 expression by suppressing miR-216b-5p expression to promotes paclitaxel resistance in the human prostate cancer.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ribosomal protein S6 kinase alpha-5 (RPS6KA5) [73]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Prostate cancer [ICD-11: 2C82]
• The Specified Disease: Prostate cancer
• The Studied Tissue: Prostate
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.96E-07; Fold-change: -1.87E-01; Z-score: -5.71E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: MSK1 signaling pathway; Inhibition; hsa04010
• In Vitro Model: PC3PR cells; Prostate; Homo sapiens (Human); CVCL_0035
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell Growth Assay
• Mechanism Description: MSk1 is a novel target gene of miR-148a in both PC3 and PC3PR cells and miR-148 attenuates paclitaxel-resistance of PC3PR cells by modulating MSk1 expression.

Head and neck cancer [ICD-11: 2D42]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Interleukin 2 receptor subunit alpha (IL2RA) [5]

• Resistant Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Head and neck cancer [ICD-11: 2D42]
• The Specified Disease: Head and neck cancer
• The Studied Tissue: Head and neck tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.41E-27; Fold-change: 2.21E-01; Z-score: 1.24E+01
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: PCI-13 cells; Ovary; Homo sapiens (Human); CVCL_C182
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: IL-2Ralpha-expressing cells were significantly more resistant to apoptosis induction by a tripeptidyl proteasome inhibitor (ALLN) and two chemotherapeutic drugs (VP-16 and taxol) than the control or IL-2Rgamma+ cells.IL-2Ralpha overexpression increases cell proliferation rate associated with increasing levels of cell cycle regulatory proteins.

Melanoma [ICD-11: 2C30]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Histone deacetylase 3 (HDAC3) [18]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Melanoma [ICD-11: 2C30]
• The Specified Disease: Melanoma
• The Studied Tissue: Skin
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.19E-01; Fold-change: -1.04E-02; Z-score: -8.20E-01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: SNU387 cells; Liver; Homo sapiens (Human); CVCL_0250
• In Vitro Model: Malme3M cells; Skin; Homo sapiens (Human); CVCL_1438
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-326, which forms a negative feedback regulatory loop with HDAC3, regulates the invasion and the metastatic potential of cancer cells and tumor-induced angiogenesis in response to anti-cancer drugs. miR-200b, miR-217, and miR-335, which form a positive feedback loop with HDAC3, confer sensitivity to anti-cancer drugs. We show that CAGE, reported to form a feedback loop with miR-200b, serves as a downstream target of HDAC3 and miR-326. In this study, we show that the regulation of the miR-326/HDAC3 axis can be employed for the development of anti-cancer therapeutics.

Bladder cancer [ICD-11: 2C94]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Hypermethylated in cancer 2 protein (HIC2) [9]

• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Bladder cancer [ICD-11: 2C94]
• The Specified Disease: Bladder cancer
• The Studied Tissue: Bladder tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.09E-01; Fold-change: -1.14E-02; Z-score: -5.19E-01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: DNA damage repair signaling pathway; Inhibition; hsa03410
• Cell Pathway Regulation: Myc/Max signaling pathway; Inhibition; hsa04218
• Cell Pathway Regulation: NF-kappaB signaling pathway; Inhibition; hsa04064
• Cell Pathway Regulation: Notch signaling pathway; Activation; hsa04330
• Cell Pathway Regulation: Oxidative stress signaling pathway; Activation; hsa00190
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: BIU87 cells; Bladder; Homo sapiens (Human); CVCL_6881
• In Vitro Model: H-bc cells; Bladder; Homo sapiens (Human); CVCL_BT00
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The DNA methylation-regulated miR-193a-3p dictates the multi-chemoresistance of bladder cancer via repression of SRSF2/PLAU/HIC2 expression.

Pancreatic cancer [ICD-11: 2C10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Protein salvador homolog 1 (SAV1) [22]

• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic cancer
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.63E-01; Fold-change: -3.55E-02; Z-score: -1.45E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Hippo signaling pathway; Regulation; N.A.
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.

Key Molecule: Serine/threonine-protein kinase LATS2 (LATS2) [22]

• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Hippo signaling pathway; Regulation; N.A.
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.

Key Molecule: MOB kinase activator 1A (MOB1A) [22]

• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Hippo signaling pathway; Regulation; N.A.
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.

Key Molecule: Serine/threonine-protein kinase 4 (MST1) [22]

• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Hippo signaling pathway; Regulation; N.A.
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-181c [22]

• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Hippo signaling pathway; Regulation; N.A.
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-let-7b [92]

• Sensitive Disease: KRAS mutant pancreatic ductal adenocarcinoma [ICD-11: 2C10.5]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: MEK/ERK /PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Let-7b repletion selectively sensitized kRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type kRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEk/ERk and PI3k/AkT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in kRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of beta-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of kRAS mutant tumors.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ribonucleoside-diphosphate reductase subunit M2 (RRM2) [92]

• Sensitive Disease: KRAS mutant pancreatic ductal adenocarcinoma [ICD-11: 2C10.5]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: MEK/ERK /PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Let-7b repletion selectively sensitized kRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type kRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEk/ERk and PI3k/AkT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in kRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of beta-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of kRAS mutant tumors.

Key Molecule: Tubulin beta-3 chain (TUBB3) [92]

• Sensitive Disease: KRAS mutant pancreatic ductal adenocarcinoma [ICD-11: 2C10.5]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: MEK/ERK /PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Let-7b repletion selectively sensitized kRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type kRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEk/ERk and PI3k/AkT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in kRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of beta-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of kRAS mutant tumors.

Oral squamous cell carcinoma [ICD-11: 2B6E]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [60]

• Sensitive Disease: Squamous cell carcinoma [ICD-11: 2B6E.3]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Oral squamous cell carcinoma [ICD-11: 2B6E]
• The Specified Disease: Oral cancer
• The Studied Tissue: Oral tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.68E-03; Fold-change: -3.93E-02; Z-score: -3.14E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KB-3-1 cells; Lung; Homo sapiens (Human); CVCL_2088
• In Vitro Model: KB-8-5 cells; Mouth; Homo sapiens (Human); CVCL_5994
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The continuous administration of low dose 5FU with Taxol significantly inhibited the tumor growth. The treatment overcomes drug resistance in tumors by down-regulating multi-drug resistance transporter protein.

Gastric cancer [ICD-11: 2B72]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Tumor protein p53-inducible nuclear protein 1 (TP53INP1) [63]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Gastric cancer [ICD-11: 2B72]
• The Specified Disease: Gastric cancer
• The Studied Tissue: Gastric tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.90E-01; Fold-change: -6.41E-02; Z-score: -8.39E-01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Exosomal delivery of miR 155 5p may induce EMT and chemoresistant phenotypes from paclitaxel resistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression.

Key Molecule: hsa-miR-155-5p [63]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Exosomal delivery of miR 155 5p may induce EMT and chemoresistant phenotypes from paclitaxel resistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression.

Key Molecule: Trans-acting T-cell-specific transcription factor GATA-3 (GATA3) [63]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Exosomal delivery of miR 155 5p may induce EMT and chemoresistant phenotypes from paclitaxel resistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression.

Key Molecule: Catenin beta-1 (CTNNB1) [88]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Regulation; N.A.
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Transwell assay; Flow cytometry assay
• Mechanism Description: Silencing of ZFAS1 augmented the sensitivity to cis-platinum or paclitaxel in gastric cancer cancer cells and silencing of ZFAS1-induced inhibition of malignancies was reversed by beta-catenin.

Key Molecule: ZNFX1 antisense RNA 1 (ZFAS1) [88]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Wnt/Beta-catenin signaling pathway; Regulation; N.A.
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay; Transwell assay; Flow cytometry assay
• Mechanism Description: Silencing of ZFAS1 augmented the sensitivity to cis-platinum or paclitaxel in gastric cancer cancer cells and silencing of ZFAS1-induced inhibition of malignancies was reversed by beta-catenin.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Microtubule-associated protein tau (MAPT) [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Gastric cancer [ICD-11: 2B72]
• The Specified Disease: Gastric cancer
• The Studied Tissue: Gastric tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.68E-01; Fold-change: -1.33E-01; Z-score: -8.88E-01
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MAPT is a microtubule-associated protein which promotes the assembly of tubulin into microtubules to stabilize microtubule structure. Reduced expression of MAPT has been also associated with a better response to paclitaxel in gastric cancer patients, reduced expression of miR-34c-5p, provides a possible mechanism of paclitaxel resistance in gastric cancer, overexpression of miR-34c-5p reduces MAPT expression and restores paclitaxel sensitivity.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Protein lin-28 homolog A (CSDD1) [87]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; N.A.
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: Protein lin-28 homolog B (CSDD2) [87]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; N.A.
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-miR-107 [87]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Lin28/miR107 pathway; Regulation; N.A.
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Lin28 could inhibit the expression of miR-107, thereby up-regulating C-myc, P-gp and down-regulating Cyclin D1, subsequently result in chemo-resistance of gastric cancer cells. The Lin28/miR-107 pathway might be served as one of many signaling pathways that is associated with gastric cancer chemo-resistance.

Key Molecule: hsa-miR-34c-5p [69]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MAPT is a microtubule-associated protein which promotes the assembly of tubulin into microtubules to stabilize microtubule structure. Reduced expression of MAPT has been also associated with a better response to paclitaxel in gastric cancer patients, reduced expression of miR-34c-5p, provides a possible mechanism of paclitaxel resistance in gastric cancer, overexpression of miR-34c-5p reduces MAPT expression and restores paclitaxel sensitivity.

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-590-5p [16]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/ERK signaling pathway; Activation; hsa04010
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay; Matrigel transwell assay
• Mechanism Description: miR590-5p regulates gastric cancer cell growth and chemosensitivity through RECk and the AkT/ERk pathway. RECk is a direct target of miR590-5p, knockdown of RECk accelerated cell proliferation and motility and decreased the drug sensitivity.The AkT/ERk and STAT3 signaling pathways were activated by miR590-5p overexpression.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) [16]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/ERK signaling pathway; Activation; hsa04010
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MkN28 cells; Gastric; Homo sapiens (Human); CVCL_1416
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Matrigel transwell assay
• Mechanism Description: miR590-5p regulates gastric cancer cell growth and chemosensitivity through RECk and the AkT/ERk pathway. RECk is a direct target of miR590-5p, knockdown of RECk accelerated cell proliferation and motility and decreased the drug sensitivity.The AkT/ERk and STAT3 signaling pathways were activated by miR590-5p overexpression.

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Programmed cell death 1 ligand 1 (PD-L1) [72]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Brain cancer [ICD-11: 2A00]
• The Specified Disease: Neuroectodermal tumor
• The Studied Tissue: Brainstem tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.63E-05; Fold-change: -1.58E-01; Z-score: -6.10E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR34a/PD-L1 signaling pathway; Regulation; N.A.
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: U87-P cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: Western blot analysis; Luciferase reporter assay
• Experiment for Drug Resistance: Annexin V/PI apoptosis assay; Cell cycle assay; MTT assay
• Mechanism Description: miR34a attenuates glioma cells progression and chemoresistance via targeting PD-L1.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-34 [72]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR34a/PD-L1 signaling pathway; Regulation; N.A.
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: U87-P cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Annexin V/PI apoptosis assay; Cell cycle assay; MTT assay
• Mechanism Description: miR34a attenuates glioma cells progression and chemoresistance via targeting PD-L1.

Key Molecule: hsa-mir-21 [76]

• Sensitive Disease: Glioblastoma [ICD-11: 2A00.02]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: EGFR/STAT3 signaling pathway; Inhibition; hsa01521
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: LN229 cells; Brain; Homo sapiens (Human); CVCL_0393
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The miR-21 inhibitor could enhance the chemo-sensitivity of human glioblastoma cells to taxol. A combination of miR-21 inhibitor and taxol could be an effective therapeutic strategy for controlling the growth of GBM by inhibiting STAT3 expression and phosphorylation.

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-495 [77]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780C cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780DX5 cells; Ovary; Homo sapiens (Human); CVCL_4T98
• In Vitro Model: SGC7901R cells; Uterus; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: Annexin-V-FITC apoptosis detection assay; Caspase-3 activity assay; MTT assay; Trypan blue exclusion assay
• Mechanism Description: miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression, miR-495 was predicted to target ABCB1, which encodes protein MDR1.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [77]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780C cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780DX5 cells; Ovary; Homo sapiens (Human); CVCL_4T98
• In Vitro Model: SGC7901R cells; Uterus; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Annexin-V-FITC apoptosis detection assay; Caspase-3 activity assay; MTT assay; Trypan blue exclusion assay
• Mechanism Description: miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression, miR-495 was predicted to target ABCB1, which encodes protein MDR1.

Osteosarcoma [ICD-11: 2B51]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Mitosis associated long intergenic non-coding RNA 1 (MALINC1) [20]

• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Silencing of MA-linc1 in unsynchronized cells results in fewer cells in G1 and a concomitant increase in the number of cells in all other stages of the cell cycle, particularly in G2/M. Moreover, its silencing in M phase-arrested cells inhibits mitosis exit. The effect of MA-linc1 on cell cycle progression is mediated, at least in part, by repression of its neighboring gene, Puralpha, a cell cycle regulator whose expression induces cell cycle arrest. Importantly, high levels of MA-linc1 are correlated with decreased survival of breast and lung cancer patients and its silencing sensitizes cancer cells to the apoptotic effect of the M phase specific chemotherapeutic drug, Paclitaxel. This enhancement of Paclitaxel-induced apoptosis is also Puralpha-related.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Transcriptional activator protein Pur-alpha (PURA) [20]

• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: Silencing of MA-linc1 in unsynchronized cells results in fewer cells in G1 and a concomitant increase in the number of cells in all other stages of the cell cycle, particularly in G2/M. Moreover, its silencing in M phase-arrested cells inhibits mitosis exit. The effect of MA-linc1 on cell cycle progression is mediated, at least in part, by repression of its neighboring gene, Puralpha, a cell cycle regulator whose expression induces cell cycle arrest. Importantly, high levels of MA-linc1 are correlated with decreased survival of breast and lung cancer patients and its silencing sensitizes cancer cells to the apoptotic effect of the M phase specific chemotherapeutic drug, Paclitaxel. This enhancement of Paclitaxel-induced apoptosis is also Puralpha-related.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-422a [78]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HFOB cells; Bone; Homo sapiens (Human); CVCL_3708
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis of apoptosis; Transwell assay
• Mechanism Description: Overexpression of miR422a inhibits cell proliferation and invasion, and enhances chemosensitivity by directly targeting TGFbeta2 in osteosarcoma cells.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Transforming growth factor beta-2 proprotein (TGFB2) [78]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HFOB cells; Bone; Homo sapiens (Human); CVCL_3708
• Experiment for Molecule Alteration: Western blot analysis; Dual luciferase activity assay
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis of apoptosis; Transwell assay
• Mechanism Description: Overexpression of miR422a inhibits cell proliferation and invasion, and enhances chemosensitivity by directly targeting TGFbeta2 in osteosarcoma cells.

Epithelial ovarian cancer [ICD-11: 2B5D]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA 1118 (LINC01118) [79]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: COC1 cells; Ovary; Homo sapiens (Human); CVCL_6891
• In Vitro Model: SkOV3-TR30 cells; Ovary; Homo sapiens (Human); CVCL_0532
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTS assay; Flow cytometry assay
• Mechanism Description: LINC01118 Can enhance ABCC1 expression by suppressing miR-134 expression to promote paclitaxel resistance in epithelial ovarian cancer.

Key Molecule: hsa-mir-134 [79]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: COC1 cells; Ovary; Homo sapiens (Human); CVCL_6891
• In Vitro Model: SkOV3-TR30 cells; Ovary; Homo sapiens (Human); CVCL_0532
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTS assay; Flow cytometry assay
• Mechanism Description: LINC01118 Can enhance ABCC1 expression by suppressing miR-134 expression to promote paclitaxel resistance in epithelial ovarian cancer.

Key Molecule: hsa-mir-520g [14]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: MAPK/AKT signaling pathway; Regulation; N.A.
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: CAOV3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• In Vitro Model: OVCA433 cells; Ovary; Homo sapiens (Human); CVCL_0475
• In Vitro Model: OV2008 cells; Ovary; Homo sapiens (Human); CVCL_0473
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: MCAS cells; Ovary; Homo sapiens (Human); CVCL_3020
• In Vitro Model: OVk18 cells; Ovary; Homo sapiens (Human); CVCL_3770
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-520g expression is significantly increased in EOC and high miR-520g expression promotes tumor development, increases chemoresistance to platinum-based chemotherapy and reduces patient survival. miR-520g directly targets and downregulates DAPk2 by binding the DAPk2 3'UTR. DAPk2 suppression, followed by MAPk and AkT pathway activation, promotes the biological processes mediated by miR-520g in EOC.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [79]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: COC1 cells; Ovary; Homo sapiens (Human); CVCL_6891
• In Vitro Model: SkOV3-TR30 cells; Ovary; Homo sapiens (Human); CVCL_0532
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTS assay; Flow cytometry assay
• Mechanism Description: LINC01118 Can enhance ABCC1 expression by suppressing miR-134 expression to promote paclitaxel resistance in epithelial ovarian cancer.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [80]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Phosphorylation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SKOV-3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: OVCAR-3 cells; Ascites; Homo sapiens (Human); CVCL_0465
• In Vitro Model: OVCAR5 cells; Ovary; Homo sapiens (Human); CVCL_1628
• In Vitro Model: OVCAR8 cells; Ovary; Homo sapiens (Human); CVCL_1629
• Mechanism Description: We show that the addition of AAFs to the culture media of EOC cell lines has the potential to induce resistance to standard-of-care drugs (SCDs). We also show that AAFs induce time- and concentration-dependent activation of downstream signalling to signal transducer and activator of transcription 3 (STAT3), and concomitantly altered phosphorylation of mitogen-activated protein kinase kinase (MEK), phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) and nuclear factor NF-kappa-B (NFkappaB). Antibodies targeting the interleukin-6 receptor (IL6R) effectively blocked phosphorylation of STAT3 and STAT1.

Key Molecule: Signal transducer activator transcription 3 (STAT3) [80]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Phosphorylation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SKOV-3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: OVCAR-3 cells; Ascites; Homo sapiens (Human); CVCL_0465
• In Vitro Model: OVCAR5 cells; Ovary; Homo sapiens (Human); CVCL_1628
• In Vitro Model: OVCAR8 cells; Ovary; Homo sapiens (Human); CVCL_1629
• Mechanism Description: We show that the addition of AAFs to the culture media of EOC cell lines has the potential to induce resistance to standard-of-care drugs (SCDs). We also show that AAFs induce time- and concentration-dependent activation of downstream signalling to signal transducer and activator of transcription 3 (STAT3), and concomitantly altered phosphorylation of mitogen-activated protein kinase kinase (MEK), phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) and nuclear factor NF-kappa-B (NFkappaB). Antibodies targeting the interleukin-6 receptor (IL6R) effectively blocked phosphorylation of STAT3 and STAT1.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Death-associated protein kinase 2 (DAPK2) [14]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: MAPK/AKT signaling pathway; Regulation; N.A.
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: CAOV3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• In Vitro Model: OVCA433 cells; Ovary; Homo sapiens (Human); CVCL_0475
• In Vitro Model: OV2008 cells; Ovary; Homo sapiens (Human); CVCL_0473
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: MCAS cells; Ovary; Homo sapiens (Human); CVCL_3020
• In Vitro Model: OVk18 cells; Ovary; Homo sapiens (Human); CVCL_3770
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-520g expression is significantly increased in EOC and high miR-520g expression promotes tumor development, increases chemoresistance to platinum-based chemotherapy and reduces patient survival. miR-520g directly targets and downregulates DAPk2 by binding the DAPk2 3'UTR. DAPk2 suppression, followed by MAPk and AkT pathway activation, promotes the biological processes mediated by miR-520g in EOC.

Key Molecule: CD109 antigen (CD109) [81]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: STAT3 signaling pathway; Activation; hsa04550
• Cell Pathway Regulation: Notch signaling pathway; Activation; hsa04330
• In Vitro Model: A2780/R cells; ovarian; Homo sapiens (Human); CVCL_4862
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: We found that CD109 expression was upregulated in doxorubicin-resistant EOC cells (A2780-R) compared with that in their parental cells. CD109 plays a key role in the acquisition of drug resistance by activating the STAT3-NOTCH1 signaling axis in patients with EOC.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-146a [66]

• Sensitive Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: miR146a/SOD2/ROS signaling pathway; Regulation; N.A.
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: PLC cells; Liver; Homo sapiens (Human); CVCL_0485
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; CCK8 assay
• Mechanism Description: miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and (+) sensitivity to chemotherapy.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Superoxide dismutase Mn (SODM) [66]

• Sensitive Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: miR146a/SOD2/ROS signaling pathway; Regulation; N.A.
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: PLC cells; Liver; Homo sapiens (Human); CVCL_0485
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; CCK8 assay
• Mechanism Description: miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and (+) sensitivity to chemotherapy.

Nasopharyngeal cancer [ICD-11: 2B6B]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: ENSG00000247844 (CCAT1) [19]

• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: CCAT1/miR181a/CPEB2 signaling pathway; Regulation; N.A.
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Upregulated CCAT1 sponges miR181a in NPC cells, and miR181a could directly bind to CCAT1 mRNA in NPC cells. Restoration of miR181a re-sensitized the NPC cells to paclitaxel in vitro, miR181a was a modulator of paclitaxel sensitivity due to its regulative effect on cell apoptosis via targeting CPEB2 in NPC cells.

Key Molecule: ENSG00000247844 (CCAT1) [19]

• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: CCAT1 reduced the sensitivity of NPC cells to paclitaxel by suppressing miR181a level and subsequently regulating CPEB2 to monitor NPC cell growth.

Key Molecule: hsa-mir-29a [82]

• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: JAKT/STAT signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Tumorigenesis; Activation; hsa05206
• In Vitro Model: NP69 cells; Nasopharynx; Homo sapiens (Human); CVCL_F755
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR-29a down-regulation is correlated with drug resistance of nasopharyngeal carcinoma cell line CNE-1 and miR-29a up-regulation decreases Taxol resistance of nasopharyngeal carcinoma CNE-1 cells possibly via inhibiting STAT3 and Bcl-2 expression.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cytoplasmic polyadenylation element-binding protein 2 (CPEB2) [19]

• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: CCAT1 reduced the sensitivity of NPC cells to paclitaxel by suppressing miR181a level and subsequently regulating CPEB2 to monitor NPC cell growth.

Key Molecule: Signal transducer activator transcription 3 (STAT3) [82]

• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: JAKT/STAT signaling pathway; Regulation; N.A.
• In Vitro Model: NP69 cells; Nasopharynx; Homo sapiens (Human); CVCL_F755
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR-29a down-regulation is correlated with drug resistance of nasopharyngeal carcinoma cell line CNE-1 and miR-29a up-regulation decreases Taxol resistance of nasopharyngeal carcinoma CNE-1 cells possibly via inhibiting STAT3 and Bcl-2 expression.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: ENSG00000247844 (CCAT1) [19]

• Sensitive Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: CCAT1/miR181a/CPEB2 signaling pathway; Regulation; N.A.
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Upregulated CCAT1 sponges miR181a in NPC cells, and miR181a could directly bind to CCAT1 mRNA in NPC cells. Restoration of miR181a re-sensitized the NPC cells to paclitaxel in vitro, miR181a was a modulator of paclitaxel sensitivity due to its regulative effect on cell apoptosis via targeting CPEB2 in NPC cells.

Key Molecule: hsa-mir-181a [19]

• Sensitive Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: CCAT1/miR181a/CPEB2 signaling pathway; Regulation; N.A.
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: LncRNA CCAT1 regulates the sensitivity of paclitaxel in NPC cells via miR181a/CPEB2 axis. miR181a restores CCAT1-induced paclitaxel resistant in NPC cells via targeting CPEB2.

Key Molecule: hsa-mir-29c [83]

• Sensitive Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: C666-1 cells; Throat; Homo sapiens (Human); CVCL_7949
• In Vitro Model: SUNE-1 cells; Nasopharynx; Homo sapiens (Human); CVCL_6946
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Overexpression of miR-29c and knockdown of ITGB1 can resensitize drug-resistant NPC cells to Taxol and promote apoptosis.

Key Molecule: hsa-miR-1204 [84]

• Sensitive Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: 5-8F cells; Nasopharynx; Homo sapiens (Human); CVCL_C528
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vitro Model: HNE-2 cells; Nasopharynx; Homo sapiens (Human); CVCL_FA07
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assay
• Mechanism Description: miR-1204 sensitizes nasopharyngeal carcinoma cells to paclitaxel both in vitro and in vivo via inhibitsing tumor growth in vivo significantly.

Key Molecule: hsa-miR-634 [85]

• Sensitive Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-634 most significantly downregulated in the paclitaxel-resistant CNE-1/Taxol, in regulating the paclitaxel sensitivity in NPC cells. miR-634 expression in the CNE-1/Taxol cells by lentivirus infection, miR-634 re-sensitized the CNE-1/Taxol cells to paclitaxel in vitro. In xenograft mouse model, miR-634 inhibited tumor growth and (+) paclitaxel sensitivity.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cytoplasmic polyadenylation element-binding protein 2 (CPEB2) [19]

• Sensitive Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: CCAT1/miR181a/CPEB2 signaling pathway; Regulation; N.A.
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: LncRNA CCAT1 regulates the sensitivity of paclitaxel in NPC cells via miR181a/CPEB2 axis. miR181a restores CCAT1-induced paclitaxel resistant in NPC cells via targeting CPEB2.

Key Molecule: Integrin beta-1 (ITGB1) [83]

• Sensitive Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: C666-1 cells; Throat; Homo sapiens (Human); CVCL_7949
• In Vitro Model: SUNE-1 cells; Nasopharynx; Homo sapiens (Human); CVCL_6946
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Overexpression of miR-29c and knockdown of ITGB1 can resensitize drug-resistant NPC cells to Taxol and promote apoptosis.

Esophageal cancer [ICD-11: 2B70]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-193a-3p [15]

• Resistant Disease: Esophageal cancer [ICD-11: 2B70.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: KYSE150 cells; Esophagus; Homo sapiens (Human); CVCL_1348
• In Vitro Model: KYSE510 cells; Esophagus; Homo sapiens (Human); CVCL_1354
• In Vitro Model: kYSE410 cells; Esophagus; Homo sapiens (Human); CVCL_1352
• In Vitro Model: kYSE450 cells; Esophagus; Homo sapiens (Human); CVCL_1353
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Presenilin-1 (PSEN1) [15]

• Resistant Disease: Esophageal cancer [ICD-11: 2B70.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: KYSE150 cells; Esophagus; Homo sapiens (Human); CVCL_1348
• In Vitro Model: KYSE510 cells; Esophagus; Homo sapiens (Human); CVCL_1354
• In Vitro Model: kYSE410 cells; Esophagus; Homo sapiens (Human); CVCL_1352
• In Vitro Model: kYSE450 cells; Esophagus; Homo sapiens (Human); CVCL_1353
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E) [86]

• Sensitive Disease: Oesophagus adenocarcinoma [ICD-11: 2B70.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Ferroptosis signaling pathway; Activation; hsa04216
• In Vitro Model: KYSE150 cells; Esophagus; Homo sapiens (Human); CVCL_1348
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay
• Mechanism Description: Repression of ANP32E increases the responsiveness of EC to PTX, and the concurrent use of erastin with PTX enhances their anti-cancer effectiveness. These findings provide support for the efficacy of inducing ferroptosis as a potential therapeutic approach to enhance the cytotoxic effects of PTX. ANP32E regulates EC progression and ferroptosis through the p53/SLC7A11 axis, offering a potential molecular target for overcoming PTX resistance in EC treatment.

Key Molecule: Acidic leucine-rich nuclear phosphoprotein 32 family member E (ANP32E) [86]

• Sensitive Disease: Oesophagus adenocarcinoma [ICD-11: 2B70.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Ferroptosis signaling pathway; Activation; hsa04216
• In Vitro Model: KYSE-30 cells; Esophagus; Homo sapiens (Human); CVCL_1351
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay
• Mechanism Description: Repression of ANP32E increases the responsiveness of EC to PTX, and the concurrent use of erastin with PTX enhances their anti-cancer effectiveness. These findings provide support for the efficacy of inducing ferroptosis as a potential therapeutic approach to enhance the cytotoxic effects of PTX. ANP32E regulates EC progression and ferroptosis through the p53/SLC7A11 axis, offering a potential molecular target for overcoming PTX resistance in EC treatment.

Colorectal cancer [ICD-11: 2B91]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [12]

• Resistant Disease: Colorectal carcinoma [ICD-11: 2B91.3]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: The transient exposure to digoxin for 24 h was found to induce MDR1 mRNA in Caco-2 cells. Here, a digoxin-tolerant Caco-2 subline (Caco/DX) was newly established by the continuous exposure of Caco-2 cells to digoxin, and the effects of continuous exposure to digoxin on MDR1 were examined. The 50% growth inhibitory concentration (IC(50)) values for digoxin in Caco-2 and Caco/DX cells were 17.2 and 81.4 nM, respectively. The IC(50) values for paclitaxel, an MDR1 substrate, were 1.0 and 547 nM, respectively, whereas the cytotoxicity of 5-fluorouracil was comparable in both.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-15 [90]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Inhibition of LINC00473 in vivo could overcome the Taxol resistance of CRC cells, could recover the expression of tumor suppressor miR-15a and chemotherapy-induced tumor regression while the BCL-2-related anti-apoptosis pathway was activated and the multidrug-resistant (MDR) genes LRP, MDR1 were up-regulated by LINC00473.

Key Molecule: Long non-protein coding RNA (LINC00473) [90]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Inhibition of LINC00473 in vivo could overcome the Taxol resistance of CRC cells, could recover the expression of tumor suppressor miR-15a and chemotherapy-induced tumor regression while the BCL-2-related anti-apoptosis pathway was activated and the multidrug-resistant (MDR) genes LRP, MDR1 were up-regulated by LINC00473.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [90]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Inhibition of LINC00473 in vivo could overcome the Taxol resistance of CRC cells, could recover the expression of tumor suppressor miR-15a and chemotherapy-induced tumor regression while the BCL-2-related anti-apoptosis pathway was activated and the multidrug-resistant (MDR) genes LRP, MDR1 were up-regulated by LINC00473.

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [91]

• Sensitive Disease: Colorectal carcinoma [ICD-11: 2B91.3]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: HCT-8 cells; Colon; Homo sapiens (Human); CVCL_2478
• In Vitro Model: NIH-G185 cells; Ovary; Homo sapiens (Human); CVCL_L991
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: G185 cells were 27-135 fold more resistant to the cytotoxic drugs doxorubicin, vinblastine, colchicine and paclitaxel than the parental NIH 3T3 cells. Co-administration of TPGS enhanced the cytotoxicity of doxorubicin, vinblastine, paclitaxel, and colchicine in the G185 cells to levels comparable to the parental.

Laryngeal cancer [ICD-11: 2C23]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Polycomb complex protein BMI-1 (BMI1) [95]

• Sensitive Disease: Laryngeal cancer [ICD-11: 2C23.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEp-2 cells; Skin; Homo sapiens (Human); CVCL_1906
• In Vitro Model: AMC-HN-8 cells; Larynx; Homo sapiens (Human); CVCL_5966
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR128a decreases the expression of BMI1 and suppresses the resistance of laryngeal cancer cells to paclitaxel & cisplatin.

Key Molecule: hsa-mir-128a [95]

• Sensitive Disease: Laryngeal cancer [ICD-11: 2C23.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEp-2 cells; Skin; Homo sapiens (Human); CVCL_1906
• In Vitro Model: AMC-HN-8 cells; Larynx; Homo sapiens (Human); CVCL_5966
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR128a decreases the expression of BMI1 and suppresses the resistance of laryngeal cancer cells to paclitaxel & cisplatin.

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