Drug Information

Drug (ID: DG00045) and It's Reported Resistant Information

• Name: Sirolimus
• Synonyms: 53123-88-9; Rapamune; Rapamycin (Sirolimus); AY-22989; Rapammune; sirolimusum; WY-090217; RAPA; Antibiotic AY 22989; AY 22989; UNII-W36ZG6FT64; CCRIS 9024; CHEBI:9168; SILA 9268A; W36ZG6FT64; HSDB 7284; C51H79NO13; NSC 226080; DE-109; NCGC00021305-05; DSSTox_CID_3582; DSSTox_RID_77091; DSSTox_GSID_23582; Cypher; Supralimus; Wy 090217; Perceiva; RAP; RPM; Rapamycin from Streptomyces hygroscopicus; SIIA 9268A; LCP-Siro; MS-R001; Rapamune (TN); Rapamycin (TN); Sirolimus (RAPAMUNE); Rapamycin C-7, analog 4; Sirolimus (USAN/INN); Sirolimus [USAN:BAN:INN]; Sirolimus, Rapamune,Rapamycin; Heptadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy; 23,27-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine; 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine; 23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29; 3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone; Sirolimus (MTOR inhibitor)
• Indication:
  In total 3 Indication(s)
  Multiple myeloma [ICD-11: 2A83]; Approved; [1]
  Transplant rejection [ICD-11: NE84]; Approved; [1]
  Hydrocephalus [ICD-11: 8D64]; Phase 1/2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [2]
  Chordoma [ICD-11: 2B5J]; [4]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (3 diseases)
  Breast cancer [ICD-11: 2C60]; [3]
  Bladder cancer [ICD-11: 2C94]; [5]
  Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]; [6]
• Target: PI3K/AKT/mTOR pathway (PAm pathway); NOUNIPROTAC; [1]
• Target: Serine/threonine-protein kinase mTOR (mTOR); MTOR_HUMAN; [1]
• Formula: C51H79NO13
• IsoSMILES: C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)O)C)/C)O)OC)C)C)/C)OC
• InChI: 1S/C51H79NO13/c1-30-16-12-11-13-17-31(2)42(61-8)28-38-21-19-36(7)51(60,65-38)48(57)49(58)52-23-15-14-18-39(52)50(59)64-43(33(4)26-37-20-22-40(53)44(27-37)62-9)29-41(54)32(3)25-35(6)46(56)47(63-10)45(55)34(5)24-30/h11-13,16-17,25,30,32-34,36-40,42-44,46-47,53,56,60H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,31-17+,35-25+/t30-,32-,33-,34-,36-,37+,38+,39+,40-,42+,43+,44-,46-,47+,51-/m1/s1
• InChIKey: QFJCIRLUMZQUOT-HPLJOQBZSA-N
• PubChem CID: 5284616
• ChEBI ID: CHEBI:9168
• TTD Drug ID: D03LJR
• VARIDT ID: DR00262
• INTEDE ID: DR1489
• DrugBank ID: DB00877

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  MRAP: Metabolic Reprogramming via Altered Pathways

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Bladder cancer [ICD-11: 2C94]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) [5]

• 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: 9.18E-02; Fold-change: -2.70E-02; Z-score: -1.91E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: EJ cells; Bladder; Homo sapiens (Human); CVCL_UI82
• In Vitro Model: J82 cells; Bladder; Homo sapiens (Human); CVCL_0359
• In Vitro Model: SV-HUC-1 cells; Bladder; Homo sapiens (Human); CVCL_3798
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: HT1376 cells; Bladder; Homo sapiens (Human); CVCL_1292
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: UCA1 knockdown suppresses growth, migration, and invasion of T24 and 5637 cells via derepression of miR-582-5p and ATG7 was downregulated by UCA1 shRNA and upregulated by miR-582-5p inhibitor.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-582-5p [5]

• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: EJ cells; Bladder; Homo sapiens (Human); CVCL_UI82
• In Vitro Model: J82 cells; Bladder; Homo sapiens (Human); CVCL_0359
• In Vitro Model: SV-HUC-1 cells; Bladder; Homo sapiens (Human); CVCL_3798
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: HT1376 cells; Bladder; Homo sapiens (Human); CVCL_1292
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: UCA1 knockdown suppresses growth, migration, and invasion of T24 and 5637 cells via derepression of miR-582-5p and ATG7 was downregulated by UCA1 shRNA and upregulated by miR-582-5p inhibitor.

Key Molecule: Urothelial cancer associated 1 (UCA1) [5]

• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: EJ cells; Bladder; Homo sapiens (Human); CVCL_UI82
• In Vitro Model: J82 cells; Bladder; Homo sapiens (Human); CVCL_0359
• In Vitro Model: SV-HUC-1 cells; Bladder; Homo sapiens (Human); CVCL_3798
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: HT1376 cells; Bladder; Homo sapiens (Human); CVCL_1292
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: UCA1 knockdown suppresses growth, migration, and invasion of T24 and 5637 cells via derepression of miR-582-5p and ATG7 was downregulated by UCA1 shRNA and upregulated by miR-582-5p inhibitor.

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Mechanistic target of rapamycin complex 1 (mTORC1) [7]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Neuroblastoma [ICD-11: 2AOO.11]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: The nude, athymic female mice, with IMR-32 or SK-N-DZ cells; Mice
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Besides both a block of glycolysis and OXPHOS, the HDAC/mTORC1 inhibitor combination produced significantly higher levels of reactive oxygen species (ROS) in the treated cells and in xenograft tumor samples, also a consequence of increased glycolytic block. The lead compounds were also tested for changes in the message levels of the glycolytic enzymes and their pathway activity, and HK2 and GPI glycolytic enzymes were most affected at their RNA message level.

Acute myeloid leukemia [ICD-11: 2A60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cysteine and glycine-rich protein 1 (CSRP1) [8]

• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Rap1 signaling pathway; Activation; hsa04015
• Cell Pathway Regulation: HIF-1 signaling pathway; Activation; hsa04066
• Cell Pathway Regulation: JAK-STAT signaling pathway; Activation; hsa04630
• In Vivo Model: Patient-derived advanced AML model; Homo sapiens
• Experiment for Drug Resistance: OncoPredict assay
• Mechanism Description: Based on the findings, the high?CSRP1?groups of patients in the TCGA datasets showed higher sensitivity to 5-fluorouracil, gemcitabine, rapamycin, and cisplatin and lower sensitivity to fludarabine. CSRP1 may serve as a potential prognostic marker and a therapeutic target for AML in the future.

Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Growth arrest specific 5 (GAS5) [6]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• 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 proliferation; Activation; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Regulation; N.A.
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Nigrosin exclusion analysis
• Mechanism Description: Small interfering RNAs (sirRNAs) targeting GAS5 protect the cell viability and proliferation of jeko-1 and z-138 cells from the inhibitory effects of mTOR inhibitors result in rapamycin resistance.

Key Molecule: Growth arrest specific 5 (GAS5) [6]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• 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 proliferation; Activation; hsa05200
• Cell Pathway Regulation: mTOR signaling pathway; Regulation; N.A.
• In Vitro Model: Z138 cells; Peripheral blood; Homo sapiens (Human); CVCL_B077
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Nigrosin exclusion analysis
• Mechanism Description: Small interfering RNAs (sirRNAs) targeting GAS5 protect the cell viability and proliferation of jeko-1 and z-138 cells from the inhibitory effects of mTOR inhibitors result in rapamycin resistance.

Osteosarcoma [ICD-11: 2B51]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-410 [1]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HFob 1.19; Bone; Homo sapiens (Human); CVCL_3708
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-410 regulates autophagy-related gene ATG16L1 expression and enhances chemosensitivity via autophagy inhibition in osteosarcoma, miR410 directly decreased ATG16L1 expression by targeting its 3'-untranslated region.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Autophagy-related protein 16-1 (ATG16L1) [1]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HFob 1.19; Bone; Homo sapiens (Human); CVCL_3708
• Experiment for Molecule Alteration: Luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA-410 regulates autophagy-related gene ATG16L1 expression and enhances chemosensitivity via autophagy inhibition in osteosarcoma, miR410 directly decreased ATG16L1 expression by targeting its 3'-untranslated region.

Chordoma [ICD-11: 2B5J]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Y-box-binding protein 1 (YBX1) [4]

• Resistant Disease: Chordoma [ICD-11: 2B5J.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR/AKT signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: Chordoma tissue; N.A.
• In Vivo Model: NOD/SCID/IL2Rgamma null (NOG) mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: YBX1 regulated protein expression of pEGFR, pAKT and its downstream target genes that influenced cell apoptosis, cell cycle transition and cell invasion. YBX1 activated the EGFR/AKT pathway in chordoma and YBX1-induced elevated expression of key molecules in the EGFR/AKT pathway were downregulated by EGFR and AKT pathway inhibitors. These in vitro results were further confirmed by in vivo data. These data showed that YBX1 promoted tumorigenesis and progression in spinal chordoma via the EGFR/AKT pathway. YBX1 might serve as a prognostic and predictive biomarker, as well as a rational therapeutic target, for chordoma.

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase mTOR (mTOR) [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Missense mutation; p.F2108L
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PIk3CA/AKT/mTOR signaling pathway; Activation; hsa04211
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• Experiment for Molecule Alteration: Integrated Mutation Profiling of Actionable Cancer Targets assay; Sanger sequencing assay
• Experiment for Drug Resistance: CellTiter-Glo luminescent cell viability assay
• Mechanism Description: The clinical relevance of these mutations is supported by a case report of a patient who acquired the identical F2108L mTOR mutation after relapse under everolimus treatment.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Nuclear receptor subfamily 6 group A member 1 (NR6A1) [3]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Molecule Alteration: Epigenetic modification; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay; Immunoblotting assay assay
• Mechanism Description: Resistance to tamoxifen and rapamycin is associated with the suppression of DNMT3A.Suppresses ERalpha activity, induces partial resistance to rapamycin and tamoxifen, and slightly decreases DNMT3A expression, indicating a functional interplay between NR6A1 and DNMT3A signaling. The development of cross-resistance in breast cancer cells to hormonal and targeted therapies involves a shift in cell signaling to alternative AKT pathways, marked by a localized suppression of the NR6A1/DNMT3A axis and associated DNA methylation changes.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) [9]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: High nuclear EDD expression in a cohort of 151 women with serous ovarian carcinoma was associated with an increased risk of disease recurrence following first-line chemotherapy, and siRNA-knockdown of EDD gene expression partially restored cisplatin sensitivity in cisplatin-resistant ovarian cancer cells in vitro. Loss of EDD induced cell-cycle arrest at G1 through upregulation of tumour suppressor p53 and p21 proteins in osteosarcoma cells in vitro.

Key Molecule: Nuclear receptor subfamily 6 group A member 1 (NR6A1) [3]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NR6A1/DNMT3A signaling pathway; Regulation; N.A.
• In Vitro Model: MCF7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay; Immunoblotting assay assay
• Mechanism Description: Resistance to tamoxifen and rapamycin is associated with the suppression of DNMT3A.Suppresses ERalpha activity, induces partial resistance to rapamycin and tamoxifen, and slightly decreases DNMT3A expression, indicating a functional interplay between NR6A1 and DNMT3A signaling. The development of cross-resistance in breast cancer cells to hormonal and targeted therapies involves a shift in cell signaling to alternative AKT pathways, marked by a localized suppression of the NR6A1/DNMT3A axis and associated DNA methylation changes.

Key Molecule: Nuclear receptor subfamily 6 group A member 1 (NR6A1) [3]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: DNMT3A signaling pathway; Regulation; N.A.
• In Vitro Model: MCF-7/Rap cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: MDA-MB-231cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Our findings indicate that the development of cross-resistance in breast cancer cells to hormonal and targeted therapies involves a shift in cell signaling to alternative AKT pathways, marked by a localized suppression of the NR6A1/DNMT3A axis and associated DNA methylation changes. We demonstrated the critical role of NR6A1 downregulation in resistance development. Additionally, we observed activation of Snail - a key regulator in the epithelial-mesenchymal transition - as a mediator of the effects of NR6A1 depletion, establishing a direct link between Snail expression and resistance formation.

Cervical cancer [ICD-11: 2C77]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-218 [10]

• Sensitive Disease: Cervical cancer [ICD-11: 2C77.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: Siha cells; Cervix uteri; Homo sapiens (Human); CVCL_0032
• In Vitro Model: Caski cells; Uterus; Homo sapiens (Human); CVCL_1100
• In Vitro Model: C33A cells; Uterus; Homo sapiens (Human); CVCL_1094
• In Vivo Model: Mouse bearing cervical cancer model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: microRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor and reducing the level of Rictor in cervical cancer.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Rapamycin-insensitive companion of mTOR (RICTOR) [10]

• Sensitive Disease: Cervical cancer [ICD-11: 2C77.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: Siha cells; Cervix uteri; Homo sapiens (Human); CVCL_0032
• In Vitro Model: Caski cells; Uterus; Homo sapiens (Human); CVCL_1100
• In Vitro Model: C33A cells; Uterus; Homo sapiens (Human); CVCL_1094
• In Vivo Model: Mouse bearing cervical cancer model; Mus musculus
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: microRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor and reducing the level of Rictor in cervical cancer.

Prostate cancer [ICD-11: 2C82]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Growth arrest specific 5 (GAS5) [11]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: 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: 22RV1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• In Vitro Model: PNT2C2 cells; Prostate; Homo sapiens (Human); CVCL_4889
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: GAS5 assay; MTS assay
• Mechanism Description: First generation mTORC1, combined mTORC1/mTORC2 and dual PI3k/mTOR inhibitors all increased cellular GAS5 levels and inhibited culture growth in androgen-dependent (LNCaP) and androgen-sensitive (22Rv1) cell lines, but not in androgen-independent (PC-3 and DU 145) cell lines. The latter exhibited low endogenous GAS5 expression, and GAS5 silencing in LNCaP and 22Rv1 cells decreased the sensitivity to mTOR inhibitors, whereas transfection of GAS5 LncRNA sensitized PC-3 and DU 145 cells to these agents.

References

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