Disease Information

General Information of the Disease (ID: DIS00073)
Name
Colorectal cancer
ICD
ICD-11: 2B91
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  ADTT: Aberration of the Drug's Therapeutic Target
  DISM: Drug Inactivation by Structure Modification
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  IDUE: Irregularity in Drug Uptake and Drug Efflux
  MRAP: Metabolic Reprogramming via Altered Pathways
  RTDM: Regulation by the Disease Microenvironment
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
15 drug(s) in total
Click to Show/Hide the Full List of Drugs
Fluorouracil
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Colorectal cancer [ICD-11: 2B91]
The Specified Disease Colorectal cancer
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 9.75E-30
Fold-change: -3.66E-01
Z-score: -1.26E+01
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
DLD1 cells Colon Homo sapiens (Human) CVCL_0248
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 A real-time cell analyzer assay
Mechanism Description c-KIT was shown to mediate chemo-resistance (kike 5-FU) in ovarian tumor initiating cells, miR-34a inhibits Erk signaling and colony formation by down-regulation of c-kit, miR-34a can inhibit this effect via down-regulation of c-kit and therefore sensitize cells to chemotherapeutic treatment.
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [2]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Colorectal cancer [ICD-11: 2B91]
The Specified Disease Colorectal cancer
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.67E-06
Fold-change: -9.64E-02
Z-score: -4.72E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
IGF-1R/AKT/S6 signaling pathway Inhibition hsa05225
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
LOVO cells Colon Homo sapiens (Human) CVCL_0399
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Ectopic expression of miR-139-5p sensitized CRC cells to 5-FU by increasing 5-FU-induced apoptosis. In addition, miR-139-5p inhibited the expression of the miR-139-5p target gene NOTCH-1 and its downstream molecules MRP-1 and BCL-2, two key MDR-associated genes. Furthermore, silencing NOTCH-1 expression promoted the chemotherapeutic effects of 5-FU, and up-regulation of NOTCH-1 abrogated miR-139-5p-mediated sensitization to 5-FU in LoVo and HCT-116 cells.
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [4]
Sensitive Disease Colorectal carcinoma [ICD-11: 2B91.3]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Colorectal cancer [ICD-11: 2B91]
The Specified Disease Colorectal carcinoma
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.67E-06
Fold-change: -9.64E-02
Z-score: -4.72E+00
Experimental Note Identified from the Human Clinical Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assay
Mechanism Description miR139-5p reverses CD44+/CD133+-associated multidrug resistance by downregulating NOTCH1 in colorectal carcinoma cells.
Key Molecule: Cadherin-1 (CDH1) [6]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Colorectal cancer [ICD-11: 2B91]
The Specified Disease Colorectal cancer
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 8.45E-01
Fold-change: 6.54E-03
Z-score: 1.95E-01
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT signaling pathway Inhibition hsa04151
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Annexin V/ PI staining; Caspase-3 activity assay
Mechanism Description Levels of PTEN and E-cadherin were reduced by knockdown of miR200c in HCT-116 cells, PTEN inactivate the AkT signaling pathway, and E-cadherin is one of the major downstream regulators of miRNA-200c contributing to EMT, which is also important to inhibit tumor invasion and proliferation as well as to induce cell apoptosis.
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: AT-rich interactive domain-containing protein 4B (ARID4B) [3]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Colorectal cancer [ICD-11: 2B91]
The Specified Disease Colorectal cancer
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 2.69E-05
Fold-change: -1.63E-01
Z-score: -4.24E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
Cell viability Inhibition hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
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 miR-519b-3p mimics promoted HCT116 and SW480 cells more sensitive to chemoradiation treatment while ectopic expression of ARID4B in the meantime decreased the sensitivity.
Key Molecule: hsa-miR-146a [14]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Mechanism Description Notably, the downregulation of hsa-miR-30a-5p and hsa-miR-146a-5p was associated with increased sensitivity to fluorouracil and oxaliplatin.
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-181b-1 [11]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PLAG1/IGF2 signaling Regulation N.A.
In Vitro Model HT-29 cells Colon Homo sapiens (Human) CVCL_0320
CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
SW620 cells Colon Homo sapiens (Human) CVCL_0547
SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
LS174T cells Colon Homo sapiens (Human) CVCL_1384
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Our previous study has identified the microRNA (miRNA) expression profile in MSI CRCs. In this study, three miRNAs (miR-181a, miR-135a and miR-302c) were validated by qRT-PCR to be dramatically decreased in 67 CRC samples. Proliferation and apoptosis assays demonstrated that miR-181a/135a/302c function as tumor suppressors via repressing PLAG1/IGF2 signaling. Moreover, we presented compelling evidence that restoration of miR-181a/135a/302c expression promoted sensitivity of MSI CRC cells to 5-FU treatment. miR-181a/135a/302c exerted their effect on chemoresistance through attenuating PLAG1 expression. Notably, the hypermethylation status of MSI CRC accounts for the decrements of miR-181a/135a/302c.
Key Molecule: hsa-miR-328 [12]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW1116 cells Colon Homo sapiens (Human) CVCL_0544
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW620 cells Colon Homo sapiens (Human) CVCL_0547
SW1116 cells Colon Homo sapiens (Human) CVCL_0544
In Vivo Model BALB/c nude xenograft model Mus musculus
Experiment for
Molecule Alteration		 Microarray assay; qRT-PCR; Western blot; luciferase assay
Experiment for
Drug Resistance		 Flow cytometry assay; Proliferation and chemosensitivity assay
Mechanism Description The level of miR-328 expression in clinical samples and its correlation with SP fraction were determined
Key Molecule: XIST [13]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation XIST/miR-30a-5p/ROR1 Regulation N.A.
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
SW620 cells Colon Homo sapiens (Human) CVCL_0547
HEK293T cells Kindey Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration		 qRT-PCR; Western blot; Dual-luciferase reporter assay
Experiment for
Drug Resistance		 MTT assay; Colony formation assay; Cell apoptosis assay
Mechanism Description This investigation was conducted to elucidate whether atractylenolide II could reverse the role of lncRNA XIST/miR-30a-5p/ROR1 axis in modulating chemosensitivity of colorectal cancer cells
Key Molecule: HOX transcript antisense RNA (HOTAIR) [55], [56]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
NF-kB signaling pathway Activation hsa04218
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description HOTAIR was associated with EZH2, which subsequently suppressed miR-218 expression, and HOTAIR contributes to 5FU resistance through suppressing miR-218 and activating NF-kB signaling in CRC. Thus, HOTAIR may serve as a promising therapeutic target for CRC patients.
Key Molecule: Long non-protein coding RNA 958 (LINC00958) [57]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model DLD1 cells Colon Homo sapiens (Human) CVCL_0248
SW620 cells Colon Homo sapiens (Human) CVCL_0547
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description BLACAT2 contributes to the cell proliferation, its levels were significantly increased in 5-fluorouracil-resistant cells, and overexpression of BLACAT2 was markedly associated with a low cell inhibition rate.
Key Molecule: hsa-mir-31 [58]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
DLD1 cells Colon Homo sapiens (Human) CVCL_0248
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Trypan blue dye-exclusion assay
Mechanism Description The increased expression level of miR-31 caused 5-FU resistance in colorectal cancer through silencing FIH-1, which is associated with cancer-specific energy metabolism.
Key Molecule: Small nucleolar RNA host gene 15 (SNHG15) [59]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
In Vivo Model BALB/c-Rag2/-IL2cc/immunodeficient mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Flow cytometry assay; Colony formation assay; MTS kit assay
Mechanism Description The levels of SNHG15 are related with the capacity of CRC cells to cope with the cytotoxic stress caused by 5-FU, which could be mediated by its interaction with AIF.
Key Molecule: GIHCG inhibitor of miR-200b/200a/429 expression (GIHCG) [60]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
Cell viability Activation hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
LOVO cells Colon Homo sapiens (Human) CVCL_0399
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description Long noncoding RNA GIHCG induces cancer progression and chemoresistance and indicates poor prognosis in colorectal cancer.
Key Molecule: piR-hsa-54265 [61]
Resistant Disease Colorectal adenocarcinoma [ICD-11: 2B91.2]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell metastasis Activation hsa05205
Cell proliferation Activation hsa05200
STAT3 signaling pathway Activation hsa04550
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assays
Mechanism Description piR-54265 binds PIWIL2 promotes CRC cell proliferation and invasiveness and 5-FU and oxaliplatin resistance via promoting oncogenic STAT3 signaling.
Key Molecule: hsa-let-7a [62]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
RkO cells Colon Homo sapiens (Human) CVCL_0504
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assay; Transwell assays and wound healing assay; Flow cytometry assay
Mechanism Description ANRIL promotes chemoresistance via disturbing expression of ABCC1 by inhibiting the expression of Let-7a in colorectal cancer.
Key Molecule: CDKN2B antisense RNA 1 (CDKN2B-AS1) [62]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
RkO cells Colon Homo sapiens (Human) CVCL_0504
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assay; Transwell assays and wound healing assay; Flow cytometry assay
Mechanism Description ANRIL promotes chemoresistance via disturbing expression of ABCC1 by regulating the expression of Let-7a in colorectal cancer.
Key Molecule: hsa-mir-218 [56]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell metastasis Activation hsa05205
NF-kB signaling pathway Activation hsa04218
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
Experiment for
Molecule Alteration		 qRT-PCR; luciferase reporter assay;ChIP
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description HOTAIR contributes to 5FU resistance through suppressing miR-218 and activating NF-kB signaling in CRC.
Key Molecule: Cytoskeleton regulator RNA (CYTOR) [63]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell metastasis Activation hsa05205
Cell proliferation Activation hsa05200
Chemoresistance Activation hsa05207
miR139-5p/Notch1 signaling pathway Regulation N.A.
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW620 cells Colon Homo sapiens (Human) CVCL_0547
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Long non-coding RNA LINC00152 promotes cell proliferation, metastasis, and confers 5-FU resistance in colorectal cancer by inhibiting miR139-5p. LINC00152 could regulate the expression of NOTCH1 through sponging miR139-5p and inhibiting its activity from promoting CRC progression and development.
Key Molecule: hsa-miR-139-5p [63]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell metastasis Activation hsa05205
Cell proliferation Activation hsa05200
miR139-5p/Notch1 signaling pathway Regulation N.A.
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW620 cells Colon Homo sapiens (Human) CVCL_0547
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Long non-coding RNA LINC00152 promotes cell proliferation, metastasis, and confers 5-FU resistance in colorectal cancer by inhibiting miR139-5p. LINC00152 could regulate the expression of NOTCH1 through sponging miR139-5p and inhibiting its activity from promoting CRC progression and development.
Key Molecule: Novel transcript, antisense to MYRFL (ENST00000547547) [64]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT116/5-FU cells Colon Homo sapiens (Human) CVCL_AU09
LOVO/5-FU cells Colon Homo sapiens (Human) CVCL_0399
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometric analysis
Mechanism Description Knockdown of miR31 increased the 5-FU sensitivity of CRC cells at least partly by upregulation of apoptosis. Overexpression of ENST00000547547 suppressed the anti-apoptotic effect of miR31 via competitive binding to it. ENST00000547547 reduces the 5-FU resistance via competitive binding to miR31 in CRC cells.
Key Molecule: hsa-mir-31 [64]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Function
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT116/5-FU cells Colon Homo sapiens (Human) CVCL_AU09
LOVO/5-FU cells Colon Homo sapiens (Human) CVCL_0399
Experiment for
Molecule Alteration		 RNA immunoprecipitation (RIP) assay; Dual-luciferase reporter assay
Experiment for
Drug Resistance		 MTT assay; Flow cytometric analysis
Mechanism Description Knockdown of miR31 increased the 5-FU sensitivity of CRC cells at least partly by upregulation of apoptosis. Overexpression of ENST00000547547 suppressed the anti-apoptotic effect of miR31 via competitive binding to it. ENST00000547547 reduces the 5-FU resistance via competitive binding to miR31 in CRC cells.
Key Molecule: HOX transcript antisense RNA (HOTAIR) [56]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation NF-kB signaling pathway Activation hsa04218
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
FHC cells Colon Homo sapiens (Human) CVCL_3688
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assays
Mechanism Description LncRNA HOTAIR contributes to 5fu resistance through suppressing miR-218 and activating NF-kB/TS signaling in colorectal cancer.
Key Molecule: hsa-mir-218 [56]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation NF-kB signaling pathway Activation hsa04218
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
FHC cells Colon Homo sapiens (Human) CVCL_3688
Experiment for
Molecule Alteration		 qPCR; Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assays
Mechanism Description LncRNA HOTAIR contributes to 5fu resistance through suppressing miR-218 and activating NF-kB/TS signaling in colorectal cancer.
Key Molecule: hsa-mir-135b [65]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT signaling pathway Activation hsa04151
In Vitro Model HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT-8/5-FU cells Colon Homo sapiens (Human) CVCL_2478
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Upregulation of microRNA-135b and microRNA-182 promotes chemoresistance of colorectal cancer by targeting ST6GALNAC2 via PI3k/AkT pathway. Inhibition of the PI3k/AkT pathway enhanced the chemosensitivity to 5-FU in HCT-8/5-FU and LoVo/5-FU.
Key Molecule: hsa-mir-182 [65]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT signaling pathway Activation hsa04151
In Vitro Model HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT-8/5-FU cells Colon Homo sapiens (Human) CVCL_2478
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Upregulation of microRNA-135b and microRNA-182 promotes chemoresistance of colorectal cancer by targeting ST6GALNAC2 via PI3k/AkT pathway. Inhibition of the PI3k/AkT pathway enhanced the chemosensitivity to 5-FU in HCT-8/5-FU and LoVo/5-FU.
Key Molecule: Sialyltransferase 7B (SIAT7B) [65]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT signaling pathway Activation hsa04151
In Vitro Model HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT-8/5-FU cells Colon Homo sapiens (Human) CVCL_2478
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Reporter gene assay; RT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Upregulation of microRNA-135b and microRNA-182 promotes chemoresistance of colorectal cancer by targeting ST6GALNAC2 via PI3k/AkT pathway. Inhibition of the PI3k/AkT pathway enhanced the chemosensitivity to 5-FU in HCT-8/5-FU and LoVo/5-FU.
Key Molecule: Long non-protein coding RNA (RP11-708H21.4) [66]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/mTOR signaling pathway Activation hsa04150
Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
DLD1 cells Colon Homo sapiens (Human) CVCL_0248
SW620 cells Colon Homo sapiens (Human) CVCL_0547
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR; Sequencing assay
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assay
Mechanism Description Overexpressed RP11-708H21.4 suppresses CRC cell proliferation through inducing G1 arrest. Moreover, up-regulation of RP11-708H21.4 inhibits cell migration and invasion, causes cell apoptosis, and enhances 5-FU sensitivity of CRC cells.
Key Molecule: hsa-mir-106a [67]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
In Vitro Model SW620 cells Colon Homo sapiens (Human) CVCL_0547
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-106a Reduces 5-Fluorouracil (5-FU) Sensitivity of Colorectal Cancer by downregulating Dual-Specificity Phosphatases 2 (DUSP2).
Key Molecule: Pvt1 oncogene (PVT1) [68]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description The overexpression of PVT1 increased the mRNA and protein expression levels of multidrug resistance associated protein 1, P glycoprotein, serine/threonine protein kinase mTOR and apoptosis regulator Bcl2.
Key Molecule: Pvt1 oncogene (PVT1) [68]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description The overexpression of PVT1 increased the mRNA and protein expression levels of multidrug resistance associated protein 1, P glycoprotein, serine/threonine protein kinase mTOR and apoptosis regulator Bcl2.
Key Molecule: hsa-miR-204-5p [69]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
UCA1/miR204-5p ceRNA signaling pathway Regulation N.A.
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p.We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.
Key Molecule: Urothelial cancer associated 1 (UCA1) [69]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
UCA1/miR204-5p ceRNA signaling pathway Regulation N.A.
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
Experiment for
Molecule Alteration		 qRT-PCR; Northern blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p.We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.
Key Molecule: Urothelial cancer associated 1 (UCA1) [69]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
UCA1/miR204-5p ceRNA signaling pathway Regulation N.A.
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
Experiment for
Molecule Alteration		 qRT-PCR; Northern blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p.We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.
Key Molecule: hsa-miR-450b-5p [70]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW620 cells Colon Homo sapiens (Human) CVCL_0547
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-450b-5p inhibited stemness and development of chemoresistance to 5-FU by targeting SOX2 in CRC cells.
Key Molecule: RAC serine/threonine-protein kinase (AKT) [71]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Phosphorylation
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
miR587/PPP2R1B/pAKT/XIAP signaling pathway Inhibition hsa05206
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
RkO cells Colon Homo sapiens (Human) CVCL_0504
FET cells Colon Homo sapiens (Human) CVCL_A604
GEO cells Colon Homo sapiens (Human) CVCL_0271
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description AkT activation mediated by PPP2R1B contributes to miR-587-conferred 5-FU resistance in colon cancer cells.
Key Molecule: hsa-miR-587 [71]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
miR587/PPP2R1B/pAKT/XIAP signaling pathway Inhibition hsa05206
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
RkO cells Colon Homo sapiens (Human) CVCL_0504
FET cells Colon Homo sapiens (Human) CVCL_A604
GEO cells Colon Homo sapiens (Human) CVCL_0271
Experiment for
Molecule Alteration		 RT-PCR; RT-qPCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description microRNA-587 antagonizes 5-FU-induced apoptosis and confers drug resistance by inhibiting PPP2R1B expression in colorectal cancer.
Key Molecule: hsa-mir-520g [72]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
p53/miR520g/p21 signaling pathway Regulation N.A.
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
RkO cells Colon Homo sapiens (Human) CVCL_0504
FET cells Colon Homo sapiens (Human) CVCL_A604
GEO cells Colon Homo sapiens (Human) CVCL_0271
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 MTT assay; ELISA assay
Mechanism Description p53 suppresses miR-520g expression and that deletion of p53 up-regulates miR-520g expression. Inhibition of miR-520g in p53 / cells increased their sensitivity to 5-FU treatment. miR-520g conferred resistance to 5-FU-induced apoptosis through the inhibition of p21 expression, which is a direct target of miR-520g. Rescued expression of p21 in miR-520g-expressing colon cancer cells sensitized them to 5-FU-induced apoptosis. Importantly, experiments in tumor xenograft mouse models demonstrate that miR-520g reduced the effectiveness of 5-FU in the inhibition of tumor growth in vivo. Moreover, studies of colorectal cancer specimens indicate a positive correlation between miR-520g expression and chemoresistance.
Key Molecule: hsa-miR-17-5p [73]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
PTEN/AKT/PI3K signaling pathway Activation hsa05235
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
COLO205 cells Colon Homo sapiens (Human) CVCL_F402
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 The expression level of miRNA-17-5p was found increased in chemoresistant patients. Significantly higher expression levels of miR-17-5p were found in CRC patients with distant metastases and higher clinical stages. kaplan-Meier analysis showed that CRC patients with higher levels of miR-17-5p had reduced survival, especially in patients who had previously received chemotherapy. Overexpression of miR-17-5p promoted COLO205 cell invasiveness. PTEN was a target of miR-17-5p in the colon cancer cells, and their context-specific interactions were responsible for multiple drug-resistance. Chemotherapy was found to increase the expression levels of miR-17-5p, which further repressed PTEN levels, contributing to the development of chemo-resistance.
Key Molecule: hsa-mir-19a [74]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Response evaluation criteria in solid tumors assay
Mechanism Description Aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.
Key Molecule: Bcl-2-like protein 11 (BCL2L11) [75]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation miR10b/BIM signaling pathway Activation hsa05206
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 Luciferase assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU.
Key Molecule: hsa-mir-10b [75]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation miR10b/BIM signaling pathway Activation hsa05206
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU.
Key Molecule: hsa-mir-21 [76]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW620 cells Colon Homo sapiens (Human) CVCL_0547
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
COLO 320DM cells Colon Homo sapiens (Human) CVCL_0219
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 FACS analysis
Mechanism Description The mismatch repair (MMR) system is involved in DNA damage recognition and repair. Human mutS homolog 2 (hMSH2) and human mutL homolog 1 (hMLH1) function as core MMR proteins and form heterodimers with protein homologs hMSH3 or hMSH6 and hMLH3 or hPMS2, respectively. Colorectal tumors that express a high level of miR-21 display reduced hMSH2 protein expression. Cells that overproduce miR-21 exhibit significantly reduced 5-fluorouracil (5-FU) -induced G2/M damage arrest and apoptosis that is characteristic of defects in the core MMR component.
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [62]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
RkO cells Colon Homo sapiens (Human) CVCL_0504
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assay; Transwell assays and wound healing assay; Flow cytometry assay
Mechanism Description ANRIL promotes chemoresistance via disturbing expression of ABCC1 by inhibiting the expression of Let-7a in colorectal cancer.
Key Molecule: ABC-type oligopeptide transporter ABCB9 (ABCB9) [64]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HCT116/5-FU cells Colon Homo sapiens (Human) CVCL_AU09
LOVO/5-FU cells Colon Homo sapiens (Human) CVCL_0399
Experiment for
Molecule Alteration		 Western blot analysis; qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometric analysis
Mechanism Description ENST00000547547 promotes ABCB9 expression by acting as a sponge of miR31 and reduces the 5-FU resistance of CRC cells.
Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [68]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description The overexpression of PVT1 increased the mRNA and protein expression levels of multidrug resistance associated protein 1, P glycoprotein, serine/threonine protein kinase mTOR and apoptosis regulator Bcl2.
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [68]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description The overexpression of PVT1 increased the mRNA and protein expression levels of multidrug resistance associated protein 1, P glycoprotein, serine/threonine protein kinase mTOR and apoptosis regulator Bcl2.
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Key Molecule: Aldolase B, fructose-bisphosphate (Aldolase B) [77]
Metabolic Type Glucose metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model CRC patients Homo Sapiens
Experiment for
Molecule Alteration		 Immunohistochemical (IHC) staining
Experiment for
Drug Resistance		 Overall survival assay (OS)
Mechanism Description This study has demonstrated that overexpression of ALDOB in CRC cells promotes lactagenesis by regulating PDK1 activation. The secreted lactate is then transported to neighboring cells and converted to pyruvate by lactate-induced LDHB, enhancing the ability of OXPHOS in terms of basal respiration and acting as a repressor of CEACAM6 expression. Consequently, ALDOB/lactate-mediated expression of CEACAM6 promotes cell proliferation and 5-FU chemoresistance in CRC cells.
Drug Sensitive Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-433 [9]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay, WST-8 assay
Mechanism Description The results indicate that miR-433 post-transcriptionally regulates the expression of TYMS mRNA and protein, and increases sensitivity to 5-FU in HeLa cells. This is the first report showing that a miRNA regulating TYMS expression has a significant impact on sensitivity to 5-FU treatment.
Key Molecule: hsa-miR-99a [9]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation mTOR signalling pathway Regulation N.A.
In Vitro Model Colorectal cancer cells Colon Homo sapiens (Human) N.A.
In Vivo Model Colorectal cancer serum samples Homo sapiens
Experiment for
Molecule Alteration		 qRT-PCR; TaqMan low-density arrays
Experiment for
Drug Resistance		 Detection of CA19-9 and CEA
Mechanism Description In this study, the expression levels of serum miRNAs in patients with CRC have been systematically determined and five serum miRNAs (miR-20a, miR-130, miR-145, miR-216 and miR-372) have been identified that are significantly upregulated in oxaliplatin-chemoresistant CRC patients compared with chemosensitive patients.
Key Molecule: hsa-miR-185 [9]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Wnt/beta-catenin signalling pathway Regulation N.A.
In Vitro Model Colorectal cancer cells Colon Homo sapiens (Human) N.A.
In Vivo Model Colorectal cancer serum samples Homo sapiens
Experiment for
Molecule Alteration		 qRT-PCR; TaqMan low-density arrays
Experiment for
Drug Resistance		 Detection of CA19-9 and CEA
Mechanism Description In this study, the expression levels of serum miRNAs in patients with CRC have been systematically determined and five serum miRNAs (miR-20a, miR-130, miR-145, miR-216 and miR-372) have been identified that are significantly upregulated in oxaliplatin-chemoresistant CRC patients compared with chemosensitive patients.
Key Molecule: hsa-miR-483 [9]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation MAPK signalling pathway Regulation N.A.
In Vitro Model Colorectal cancer cells Colon Homo sapiens (Human) N.A.
In Vivo Model Colorectal cancer serum samples Homo sapiens
Experiment for
Molecule Alteration		 qRT-PCR; TaqMan low-density arrays
Experiment for
Drug Resistance		 Detection of CA19-9 and CEA
Mechanism Description In this study, the expression levels of serum miRNAs in patients with CRC have been systematically determined and five serum miRNAs (miR-20a, miR-130, miR-145, miR-216 and miR-372) have been identified that are significantly upregulated in oxaliplatin-chemoresistant CRC patients compared with chemosensitive patients.
Vincristine
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [4]
Sensitive Disease Colorectal carcinoma [ICD-11: 2B91.3]
Sensitive Drug Vincristine
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Colorectal cancer [ICD-11: 2B91]
The Specified Disease Colorectal carcinoma
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.67E-06
Fold-change: -9.64E-02
Z-score: -4.72E+00
Experimental Note Identified from the Human Clinical Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assay
Mechanism Description miR139-5p reverses CD44+/CD133+-associated multidrug resistance by downregulating NOTCH1 in colorectal carcinoma cells.
Oxaliplatin
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [4]
Sensitive Disease Colorectal carcinoma [ICD-11: 2B91.3]
Sensitive Drug Oxaliplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Colorectal cancer [ICD-11: 2B91]
The Specified Disease Colorectal carcinoma
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.67E-06
Fold-change: -9.64E-02
Z-score: -4.72E+00
Experimental Note Identified from the Human Clinical Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Colony formation assay
Mechanism Description miR139-5p reverses CD44+/CD133+-associated multidrug resistance by downregulating NOTCH1 in colorectal carcinoma cells.
Berberine
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Cancer susceptibility 2 (CASC2) [15]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Berberine
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description LncRNA CASC2 mediates the berberine-induced pro-apoptotic effect via inhibition of Bcl-2 expression at the post-transcriptional level.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [15]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Berberine
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description LncRNA CASC2 mediates the berberine-induced pro-apoptotic effect via inhibition of Bcl-2 expression at the post-transcriptional level.
Bevacizumab
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Key Molecule: Histone H3 [16]
Metabolic Type Glucose metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Bevacizumab
 Drug Info 
Molecule Alteration Lactylation
H3K18la
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
SW620 cells Colon Homo sapiens (Human) CVCL_0547
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer.
Key Molecule: Enolase 2 (ENO2) [17]
Metabolic Type Glucose metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Bevacizumab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
SW620 cells Colon Homo sapiens (Human) CVCL_0547
In Vivo Model 6-to 8-week-old female NOD/SCID mice, with fresh tissue from patient Mice
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Here, we found that high levels of ENO2 expression and ENO2-related neuroendocrine differentiation were associated with resistance to antiangiogenic therapy in CRC. Notably, the ENO2-derived PEP was responsible for ENO2-mediated resistance to antiangiogenic therapy in CRC, and PEP enhanced beta-catenin Lys49 acetylation by selectively inhibiting histone deacetylase 1 (HDAC1) activity.
Key Molecule: Enolase 2 (ENO2) [17]
Metabolic Type Glucose metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Bevacizumab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
In Vivo Model 4-to 6-week-old female BALB/c nude mice, with HCT116vector, HCT116ENO2, HCT116shNC and HCT116shENO2, Rego-resistant SW620 or Bev-resistant HCT116 cells Mice
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Here, we found that high levels of ENO2 expression and ENO2-related neuroendocrine differentiation were associated with resistance to antiangiogenic therapy in CRC. Notably, the ENO2-derived PEP was responsible for ENO2-mediated resistance to antiangiogenic therapy in CRC, and PEP enhanced beta-catenin Lys49 acetylation by selectively inhibiting histone deacetylase 1 (HDAC1) activity.
Key Molecule: Histone H3 [16]
Metabolic Type Glucose metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Bevacizumab
 Drug Info 
Molecule Alteration Lactylation
H3K18la
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vivo Model Patient-derived xenograft (PDX) mice Mice
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Quantification viability of patient-derived organoids
Mechanism Description Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer.
Key Molecule: Histone H3 [16]
Metabolic Type Glucose metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Bevacizumab
 Drug Info 
Molecule Alteration Lactylation
H3K18la
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vivo Model Patient-derived xenograft (PDX) mice Mice
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Tumor weight assay
Mechanism Description Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer.
Key Molecule: Histone H3 [16]
Metabolic Type Glucose metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Bevacizumab
 Drug Info 
Molecule Alteration Lactylation
H3K18la
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
SW620 cells Colon Homo sapiens (Human) CVCL_0547
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Western blot assay
Mechanism Description Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer.
Cabozantinib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: VEGF-2 receptor (KDR) [18]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cabozantinib
 Drug Info 
Molecule Alteration Missense mutation
p.R1032Q (c.3095G>A)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation VEGF signaling pathway Activation hsa04370
In Vitro Model Colo-320 cells Colon Homo sapiens (Human) CVCL_1989
MDST8 cells Colon Homo sapiens (Human) CVCL_2588
In Vivo Model Nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 BEAMing assay; Western blot analysis; immunofluorescence assay
Experiment for
Drug Resistance		 Promega assay
Mechanism Description VEGFR2 is somatically mutated across tumor types and that VEGFR2 mutants can be oncogenic and control sensitivity/resistance to antiangiogenic drugs.
Cetuximab
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Epidermal growth factor receptor (EGFR) [19]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Missense mutation
p.G465E
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Colon cells Colon Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations.
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: POU class 5 homeobox 1 pseudogene 4 (POU5F1P4) [20]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
NCI-H508 cells Colon Homo sapiens (Human) CVCL_1564
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Down-regulation of POU5F1P4 decreased the sensitivity of colorectal cancer cells to cetuximab. POU5F1P4 may contribute to cetuximab resistance by interacting with protein coding genes that affect different biological pathways.
Key Molecule: Mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) [21]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Inhibition hsa04310
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
DLD1 cells Colon Homo sapiens (Human) CVCL_0248
SW620 cells Colon Homo sapiens (Human) CVCL_0547
CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
RkO cells Colon Homo sapiens (Human) CVCL_0504
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
NCI-H508 cells Colon Homo sapiens (Human) CVCL_1564
SW1116 cells Colon Homo sapiens (Human) CVCL_0544
COLO 320DM cells Colon Homo sapiens (Human) CVCL_0219
HCT15 cells Colon Homo sapiens (Human) CVCL_0292
LS174T cells Colon Homo sapiens (Human) CVCL_1384
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SW948 cells Colon Homo sapiens (Human) CVCL_0632
SW403 cells Colon Homo sapiens (Human) CVCL_0545
SW48 cells Colon Homo sapiens (Human) CVCL_1724
COLO205 cells Colon Homo sapiens (Human) CVCL_F402
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
LS123 cells Colon Homo sapiens (Human) CVCL_1383
SK-CO-1 cells Colon Homo sapiens (Human) CVCL_0626
SW837 cells Colon Homo sapiens (Human) CVCL_1729
T84 cells Colon Homo sapiens (Human) CVCL_0555
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qPCR; Sequencing assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description There is a double-negative feedback loop between MIR100HG and the transcription factor GATA6, whereby GATA6 represses MIR100HG, but this repression is relieved by miR125b targeting of GATA6.
Key Molecule: hsa-mir-100 [21]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Inhibition hsa04310
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
DLD1 cells Colon Homo sapiens (Human) CVCL_0248
SW620 cells Colon Homo sapiens (Human) CVCL_0547
CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
RkO cells Colon Homo sapiens (Human) CVCL_0504
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
NCI-H508 cells Colon Homo sapiens (Human) CVCL_1564
SW1116 cells Colon Homo sapiens (Human) CVCL_0544
COLO 320DM cells Colon Homo sapiens (Human) CVCL_0219
HCT15 cells Colon Homo sapiens (Human) CVCL_0292
LS174T cells Colon Homo sapiens (Human) CVCL_1384
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SW948 cells Colon Homo sapiens (Human) CVCL_0632
SW403 cells Colon Homo sapiens (Human) CVCL_0545
SW48 cells Colon Homo sapiens (Human) CVCL_1724
COLO205 cells Colon Homo sapiens (Human) CVCL_F402
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
LS123 cells Colon Homo sapiens (Human) CVCL_1383
SK-CO-1 cells Colon Homo sapiens (Human) CVCL_0626
SW837 cells Colon Homo sapiens (Human) CVCL_1729
T84 cells Colon Homo sapiens (Human) CVCL_0555
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Luciferase reporter assay; qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR100 and miR125b coordinately repressed five Wnt/beta-catenin negative regulators, resulting in increased Wnt signaling, and Wnt inhibition in cetuximab-resistant cells restored cetuximab responsiveness.
Key Molecule: hsa-mir-125b [21]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Inhibition hsa04310
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
DLD1 cells Colon Homo sapiens (Human) CVCL_0248
SW620 cells Colon Homo sapiens (Human) CVCL_0547
CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
RkO cells Colon Homo sapiens (Human) CVCL_0504
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
NCI-H508 cells Colon Homo sapiens (Human) CVCL_1564
SW1116 cells Colon Homo sapiens (Human) CVCL_0544
COLO 320DM cells Colon Homo sapiens (Human) CVCL_0219
HCT15 cells Colon Homo sapiens (Human) CVCL_0292
LS174T cells Colon Homo sapiens (Human) CVCL_1384
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SW948 cells Colon Homo sapiens (Human) CVCL_0632
SW403 cells Colon Homo sapiens (Human) CVCL_0545
SW48 cells Colon Homo sapiens (Human) CVCL_1724
COLO205 cells Colon Homo sapiens (Human) CVCL_F402
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
LS123 cells Colon Homo sapiens (Human) CVCL_1383
SK-CO-1 cells Colon Homo sapiens (Human) CVCL_0626
SW837 cells Colon Homo sapiens (Human) CVCL_1729
T84 cells Colon Homo sapiens (Human) CVCL_0555
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Luciferase reporter assay; qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR100 and miR125b coordinately repressed five Wnt/beta-catenin negative regulators, resulting in increased Wnt signaling, and Wnt inhibition in cetuximab-resistant cells restored cetuximab responsiveness.
Key Molecule: Mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) [21]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Activation hsa04310
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
GIST-T1 cells Gastric Homo sapiens (Human) CVCL_4976
CAL62 cells Thyroid gland Homo sapiens (Human) CVCL_1112
CAL-62 cells Thyroid gland Homo sapiens (Human) CVCL_1112
CCL-131 cells Brain Mus musculus (Mouse) CVCL_0470
COLO320DM cells Colon Homo sapiens (Human) CVCL_0219
CT26 WT cells Colon Mus musculus (Mouse) CVCL_7256
Detroit562 cells Pleural effusion Homo sapiens (Human) CVCL_1171
DIPG 007 cells Brain Homo sapiens (Human) CVCL_VU70
DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
FL83B cells Liver Mus musculus (Mouse) CVCL_4691
GH3 cells Pituitary gland Rattus norvegicus (Rat) CVCL_0273
GH4C1 cells pituitary gland Rattus norvegicus (Rat) CVCL_0276
H1650 cells Pleural effusion Homo sapiens (Human) CVCL_4V01
H9 cells Peripheral blood Homo sapiens (Human) CVCL_1240
H9/HTLV cells Peripheral blood Homo sapiens (Human) CVCL_3514
HEK 293T cells Kidney Homo sapiens (Human) CVCL_0063
HeLa S cells Uterus Homo sapiens (Human) CVCL_0058
HeLa229 cells Uterus Homo sapiens (Human) CVCL_1276
HH cells Peripheral blood Homo sapiens (Human) CVCL_1280
HPrEC cells Prostate Homo sapiens (Human) CVCL_A2EM
Human RPMI8226 myeloma cells Peripheral blood Homo sapiens (Human) CVCL_0014
KB-C2 cells Uterus Homo sapiens (Human) CVCL_D600
Experiment for
Molecule Alteration		 RT-PCR
Mechanism Description miR-100HG, miR-100 and miR-125b overexpression was also observed in cetuximab-resistant colorectal cancer and head and neck squamous cell cancer cell lines and in tumors from colorectal cancer patients that progressed on cetuximab. miR-100 and miR-125b coordinately repressed five Wnt/beta-catenin negative regulators, resulting in increased Wnt signaling, and Wnt inhibition in cetuximab-resistant cells restored cetuximab responsiveness.
Key Molecule: hsa-mir-100 [21]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Activation hsa04310
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
GIST-T1 cells Gastric Homo sapiens (Human) CVCL_4976
CAL62 cells Thyroid gland Homo sapiens (Human) CVCL_1112
CAL-62 cells Thyroid gland Homo sapiens (Human) CVCL_1112
CCL-131 cells Brain Mus musculus (Mouse) CVCL_0470
COLO320DM cells Colon Homo sapiens (Human) CVCL_0219
CT26 WT cells Colon Mus musculus (Mouse) CVCL_7256
Detroit562 cells Pleural effusion Homo sapiens (Human) CVCL_1171
DIPG 007 cells Brain Homo sapiens (Human) CVCL_VU70
DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
FL83B cells Liver Mus musculus (Mouse) CVCL_4691
GH3 cells Pituitary gland Rattus norvegicus (Rat) CVCL_0273
GH4C1 cells pituitary gland Rattus norvegicus (Rat) CVCL_0276
H1650 cells Pleural effusion Homo sapiens (Human) CVCL_4V01
H9 cells Peripheral blood Homo sapiens (Human) CVCL_1240
H9/HTLV cells Peripheral blood Homo sapiens (Human) CVCL_3514
HEK 293T cells Kidney Homo sapiens (Human) CVCL_0063
HeLa S cells Uterus Homo sapiens (Human) CVCL_0058
HeLa229 cells Uterus Homo sapiens (Human) CVCL_1276
HH cells Peripheral blood Homo sapiens (Human) CVCL_1280
HPrEC cells Prostate Homo sapiens (Human) CVCL_A2EM
Human RPMI8226 myeloma cells Peripheral blood Homo sapiens (Human) CVCL_0014
KB-C2 cells Uterus Homo sapiens (Human) CVCL_D600
Experiment for
Molecule Alteration		 RT-PCR
Mechanism Description miR-100HG, miR-100 and miR-125b overexpression was also observed in cetuximab-resistant colorectal cancer and head and neck squamous cell cancer cell lines and in tumors from colorectal cancer patients that progressed on cetuximab. miR-100 and miR-125b coordinately repressed five Wnt/beta-catenin negative regulators, resulting in increased Wnt signaling, and Wnt inhibition in cetuximab-resistant cells restored cetuximab responsiveness.
Key Molecule: hsa-mir-125b [21]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Activation hsa04310
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
GIST-T1 cells Gastric Homo sapiens (Human) CVCL_4976
CAL62 cells Thyroid gland Homo sapiens (Human) CVCL_1112
CAL-62 cells Thyroid gland Homo sapiens (Human) CVCL_1112
CCL-131 cells Brain Mus musculus (Mouse) CVCL_0470
COLO320DM cells Colon Homo sapiens (Human) CVCL_0219
CT26 WT cells Colon Mus musculus (Mouse) CVCL_7256
Detroit562 cells Pleural effusion Homo sapiens (Human) CVCL_1171
DIPG 007 cells Brain Homo sapiens (Human) CVCL_VU70
DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
FL83B cells Liver Mus musculus (Mouse) CVCL_4691
GH3 cells Pituitary gland Rattus norvegicus (Rat) CVCL_0273
GH4C1 cells pituitary gland Rattus norvegicus (Rat) CVCL_0276
H1650 cells Pleural effusion Homo sapiens (Human) CVCL_4V01
H9 cells Peripheral blood Homo sapiens (Human) CVCL_1240
H9/HTLV cells Peripheral blood Homo sapiens (Human) CVCL_3514
HEK 293T cells Kidney Homo sapiens (Human) CVCL_0063
HeLa S cells Uterus Homo sapiens (Human) CVCL_0058
HeLa229 cells Uterus Homo sapiens (Human) CVCL_1276
HH cells Peripheral blood Homo sapiens (Human) CVCL_1280
HPrEC cells Prostate Homo sapiens (Human) CVCL_A2EM
Human RPMI8226 myeloma cells Peripheral blood Homo sapiens (Human) CVCL_0014
KB-C2 cells Uterus Homo sapiens (Human) CVCL_D600
Experiment for
Molecule Alteration		 RT-PCR
Mechanism Description miR-100HG, miR-100 and miR-125b overexpression was also observed in cetuximab-resistant colorectal cancer and head and neck squamous cell cancer cell lines and in tumors from colorectal cancer patients that progressed on cetuximab. miR-100 and miR-125b coordinately repressed five Wnt/beta-catenin negative regulators, resulting in increased Wnt signaling, and Wnt inhibition in cetuximab-resistant cells restored cetuximab responsiveness.
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Key Molecule: Solute carrier family 25 member 21 (SLC25A21) [22]
Metabolic Type Glutamine metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Caco2 cells Colon Homo sapiens (Human) CVCL_0025
DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
LS 174T cells Colon Homo sapiens (Human) CVCL_1384
LOVO cells Colon Homo sapiens (Human) CVCL_0399
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Restoration of SLC25A21 expression abrogates KRAS-mutation-mediated resistance to cetuximab in CRC. KRAS mutation, which results in hyperactive PI3K/AKT and RAF/ERK signaling (26), is responsible for resistance to anti-EGFR antibody therapy (27).
Key Molecule: Solute carrier family 25 member 21 (SLC25A21) [22]
Metabolic Type Glutamine metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model M5 cells Colon Homo sapiens (Human) CVCL_WH33
SW620 cells Colon Homo sapiens (Human) CVCL_0547
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Restoration of SLC25A21 expression abrogates KRAS-mutation-mediated resistance to cetuximab in CRC. KRAS mutation, which results in hyperactive PI3K/AKT and RAF/ERK signaling (26), is responsible for resistance to anti-EGFR antibody therapy (27).
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: Programmed cell death 6-interacting protein (PDCD6IP) [23]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell colony Activation hsa05200
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description UCA1 expression was markedly higher in cetuximab-resistant cancer cells and their exosomes and the expression of TSG101, Alix, and CD81, which are all exosome markers and are associated with exosome formation, in both exosomes and cells.
Key Molecule: Urothelial cancer associated 1 (UCA1) [23]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell colony Activation hsa05200
Cell proliferation Activation hsa05200
In Vitro Model CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description UCA1 expression was markedly higher in cetuximab-resistant cancer cells and their exosomes and the expression of TSG101, Alix, and CD81, which are all exosome markers and are associated with exosome formation, in both exosomes and cells.
Key Molecule: GDH/6PGL endoplasmic bifunctional protein (H6PD) [24]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation Pentose phosphate signaling pathway Activation hsa00030
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
GEO cells Colon Homo sapiens (Human) CVCL_0271
In Vivo Model Xenografts mouse model Mus musculus
Experiment for
Molecule Alteration		 2D DIGE assay
Mechanism Description LDHB and PDHA1 were downregulated in GEO-CR tumor xenografts, similarly to the corresponding deregulations observed in the derived cell lines. Upregulation of G6PDH and transketolase (TkT) was also actually maintained in tumor xenografts. Indeed, PPP2CA expression in xenografted samples was similarly evaluated, demonstrating that protein downregulation in vivo was even more pronounced than that measured in GEO-CR cells.
Key Molecule: L-lactate dehydrogenase B chain (LDHB) [24]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation Pentose phosphate signaling pathway Activation hsa00030
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
GEO cells Colon Homo sapiens (Human) CVCL_0271
In Vivo Model Xenografts mouse model Mus musculus
Experiment for
Molecule Alteration		 2D DIGE assay
Mechanism Description LDHB and PDHA1 were downregulated in GEO-CR tumor xenografts, similarly to the corresponding deregulations observed in the derived cell lines. Upregulation of G6PDH and transketolase (TkT) was also actually maintained in tumor xenografts. Indeed, PPP2CA expression in xenografted samples was similarly evaluated, demonstrating that protein downregulation in vivo was even more pronounced than that measured in GEO-CR cells.
Key Molecule: Pyruvate dehydrogenase E1 component subunit alpha (PDHA1) [24]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation Pentose phosphate signaling pathway Activation hsa00030
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
GEO cells Colon Homo sapiens (Human) CVCL_0271
In Vivo Model Xenografts mouse model Mus musculus
Experiment for
Molecule Alteration		 2D DIGE assay
Mechanism Description LDHB and PDHA1 were downregulated in GEO-CR tumor xenografts, similarly to the corresponding deregulations observed in the derived cell lines. Upregulation of G6PDH and transketolase (TkT) was also actually maintained in tumor xenografts. Indeed, PPP2CA expression in xenografted samples was similarly evaluated, demonstrating that protein downregulation in vivo was even more pronounced than that measured in GEO-CR cells.
Key Molecule: Transketolase (TKT) [24]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Discovered Using In-vivo Testing Model
Cell Pathway Regulation Pentose phosphate signaling pathway Activation hsa00030
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
GEO cells Colon Homo sapiens (Human) CVCL_0271
In Vivo Model Xenografts mouse model Mus musculus
Experiment for
Molecule Alteration		 2D DIGE assay
Mechanism Description LDHB and PDHA1 were downregulated in GEO-CR tumor xenografts, similarly to the corresponding deregulations observed in the derived cell lines. Upregulation of G6PDH and transketolase (TkT) was also actually maintained in tumor xenografts. Indeed, PPP2CA expression in xenografted samples was similarly evaluated, demonstrating that protein downregulation in vivo was even more pronounced than that measured in GEO-CR cells.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Transcription factor GATA6 (GATA6) [21]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Chemoresistance Activation hsa05207
Wnt/Beta-catenin signaling pathway Inhibition hsa04310
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
DLD1 cells Colon Homo sapiens (Human) CVCL_0248
SW620 cells Colon Homo sapiens (Human) CVCL_0547
CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
RkO cells Colon Homo sapiens (Human) CVCL_0504
HCT8 cells Colon Homo sapiens (Human) CVCL_2478
NCI-H508 cells Colon Homo sapiens (Human) CVCL_1564
SW1116 cells Colon Homo sapiens (Human) CVCL_0544
COLO 320DM cells Colon Homo sapiens (Human) CVCL_0219
HCT15 cells Colon Homo sapiens (Human) CVCL_0292
LS174T cells Colon Homo sapiens (Human) CVCL_1384
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SW948 cells Colon Homo sapiens (Human) CVCL_0632
SW403 cells Colon Homo sapiens (Human) CVCL_0545
SW48 cells Colon Homo sapiens (Human) CVCL_1724
COLO205 cells Colon Homo sapiens (Human) CVCL_F402
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
LS123 cells Colon Homo sapiens (Human) CVCL_1383
SK-CO-1 cells Colon Homo sapiens (Human) CVCL_0626
SW837 cells Colon Homo sapiens (Human) CVCL_1729
T84 cells Colon Homo sapiens (Human) CVCL_0555
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qPCR; Sequencing assay; Western blot analysis; Immunofluorescent staining assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description There is a double-negative feedback loop between MIR100HG and the transcription factor GATA6, whereby GATA6 represses MIR100HG, but this repression is relieved by miR125b targeting of GATA6.
Key Molecule: GTPase KRas (KRAS) [19], [25], [26]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Missense mutation
p.G12V
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.98  Å
PDB: 7SCW
Mutant Type Structure Method: X-ray diffraction Resolution: 1.96  Å
PDB: 7SCX
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.47
TM score: 0.99104
Amino acid change:
G12V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
0
|
S
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
V
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
S
S
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
D
D
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
K
H
H
K
K
E
E
K
K
170
|
M
M
S
S
K
K
D
D
G
G
K
K
K
K
K
K
K
K
K
K
180
|
K
K
S
S
K
K
T
T
K
K
C
C
V
V
I
I
M
M
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation EGFR/RAS signaling pathway Activation hsa01521
In Vitro Model LIM1215 cells Colon Homo sapiens (Human) CVCL_2574
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations (27780856). kRAS and EGFR ectodomain-acquired mutations in patients with metastatic colorectal cancer (mCRC) have been correlated with acquired resistance to anti-EGFR monoclonal antibodies (mAbs).
Key Molecule: GTPase KRas (KRAS) [19]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Missense mutation
p.Q61H
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.31  Å
PDB: 6T5V
Mutant Type Structure Method: X-ray diffraction Resolution: 2.20  Å
PDB: 6MNX
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.14
TM score: 0.96411
Amino acid change:
Q61H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
C
G
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
S
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
H
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
L
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
S
C
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
D
D
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
K
H
H
K
K
E
E
K
K
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations.
Key Molecule: GTPase KRas (KRAS) [19]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Missense mutation
p.G12D
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.40  Å
PDB: 6VJJ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 8JHL
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.55
TM score: 0.9318
Amino acid change:
G12D
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
G
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
D
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
R
V
V
D
E
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
Q
H
Y
K
R
E
L
K
K
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations.
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [19]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Missense mutation
p.V600E
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.55  Å
PDB: 4E26
Mutant Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 4G9R
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.53
TM score: 0.95765
Amino acid change:
V600E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
420
|
M
M
D
D
R
R
G
G
S
S
H
H
H
H
H
H
H
H
H
H
430
|
H
H
G
G
S
S
E
E
D
D
R
R
N
N
R
R
M
M
K
K
440
|
T
T
L
L
G
G
R
R
R
R
D
D
S
S
S
S
D
D
D
D
450
|
W
W
E
E
I
I
P
P
D
D
G
G
Q
Q
I
I
T
T
V
V
460
|
G
G
Q
Q
R
R
I
I
G
G
S
S
G
G
S
S
F
F
G
G
470
|
T
T
V
V
Y
Y
K
K
G
G
K
K
W
W
H
H
G
G
D
D
480
|
V
V
A
A
V
V
K
K
M
M
L
L
N
N
V
V
T
T
A
A
490
|
P
P
T
T
P
P
Q
Q
Q
Q
L
L
Q
Q
A
A
F
F
K
K
500
|
N
N
E
E
V
V
G
G
V
V
L
L
R
R
K
K
T
T
R
R
510
|
H
H
V
V
N
N
I
I
L
L
L
L
F
F
M
M
G
G
Y
Y
520
|
S
S
T
T
K
K
P
P
Q
Q
L
L
A
A
I
I
V
V
T
T
530
|
Q
Q
W
W
C
C
E
E
G
G
S
S
S
S
L
L
Y
Y
H
H
540
|
H
H
L
L
H
H
I
I
I
I
E
E
T
T
K
K
F
F
E
E
550
|
M
M
I
I
K
K
L
L
I
I
D
D
I
I
A
A
R
R
Q
Q
560
|
T
T
A
A
Q
Q
G
G
M
M
D
D
Y
Y
L
L
H
H
A
A
570
|
K
K
S
S
I
I
I
I
H
H
R
R
D
D
L
L
K
K
S
S
580
|
N
N
N
N
I
I
F
F
L
L
H
H
E
E
D
D
L
L
T
T
590
|
V
V
K
K
I
I
G
G
D
D
F
F
G
G
L
L
A
A
T
T
600
|
V
E
K
K
S
S
R
R
W
W
S
S
G
G
S
S
H
H
Q
Q
610
|
F
F
E
E
Q
Q
L
L
S
S
G
G
S
S
I
I
L
L
W
W
620
|
M
M
A
A
P
P
E
E
V
V
I
I
R
R
M
M
Q
Q
D
D
630
|
K
K
N
N
P
P
Y
Y
S
S
F
F
Q
Q
S
S
D
D
V
V
640
|
Y
Y
A
A
F
F
G
G
I
I
V
V
L
L
Y
Y
E
E
L
L
650
|
M
M
T
T
G
G
Q
Q
L
L
P
P
Y
Y
S
S
N
N
I
I
660
|
N
N
N
N
R
R
D
D
Q
Q
I
I
I
I
F
F
M
M
V
V
670
|
G
G
R
R
G
G
Y
Y
L
L
S
S
P
P
D
D
L
L
S
S
680
|
K
K
V
V
R
R
S
S
N
N
C
C
P
P
K
K
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Colon cells Colon Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations.
Key Molecule: Hepatocyte growth factor receptor (MET) [19]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Structural variation
Amplification
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations.
Key Molecule: GTPase KRas (KRAS) [19]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Structural variation
Amplification
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations.
Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [19]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Structural variation
Amplification
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations.
Key Molecule: Hepatocyte growth factor receptor (MET) [27]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Structural variation
Copy number gain
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing analysis; Gene copy number analysis
Mechanism Description As amplification of the MET gene has recently been shown to drive resistance to anti-EGFR therapies, this copy number change is the best candidate to explain the poor treatment response.
Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [28]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Structural variation
Amplification
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; Next-generation sequencing assay
Mechanism Description Mutations in kRAS, NRAS, and BRAF and amplification of ERBB2 and MET drive primary (de novo) resistance to anti-EGFR treatment.
Key Molecule: GTPase KRas (KRAS) [29]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Mutation
Mutations in codons 12, 13 and 61
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation RAS/RAF/Mek/ERK signaling pathway Activation hsa04010
In Vitro Model Colorectal cancer cells Colon Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 High throughout experiment assay
Experiment for
Drug Resistance		 Circulating tumor DNA analysis
Mechanism Description The identification of kRAS mutations as a cause for intrinsic resistance of colorectal cancers also contributed to the identification of a mechanism for the acquired resistance. Establishment and analysis of cetuximabresistant colorectal cancer cell lines revealed that the resistant variants harbored kRAS point mutations or amplification, and the findings were confirmed in clinical specimens.
Key Molecule: Homeobox protein Hox-B8 (HOXB8) [30]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation STAT3 signaling pathway Activation hsa04550
In Vitro Model Caco2 cells Colon Homo sapiens (Human) CVCL_0025
HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 Western blot assay
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description By comparing drug-sensitive cell lines (SW48) with drug-resistant cell lines (HCT116, CACO2), we discovered that HOXB8 was substantially expressed in cetuximab-resistant cell lines, and furthermore, in drug-resistant cell lines (HCT116, CACO2), HOXB8 knockdown increased the cytotoxicity of cetuximab via blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Conversely, the excessive expression of HOXB8 reduced the growth suppression in SW48 cells caused by cetuximab by triggering the STAT3 signaling pathway. Conclusively, we conclude that HOXB8 has played an essential role in cetuximab-resistant mCRC and that treating HOXB8 specifically may be a useful treatment approach for certain cetuximab-resistant mCRC patients.
Key Molecule: Signal transducer and activator of transcription 3 (STAT3) [30]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation STAT3 signaling pathway Activation hsa04550
In Vitro Model Caco2 cells Colon Homo sapiens (Human) CVCL_0025
Experiment for
Molecule Alteration		 Western blot assay
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description By comparing drug-sensitive cell lines (SW48) with drug-resistant cell lines (HCT116, CACO2), we discovered that HOXB8 was substantially expressed in cetuximab-resistant cell lines, and furthermore, in drug-resistant cell lines (HCT116, CACO2), HOXB8 knockdown increased the cytotoxicity of cetuximab via blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Conversely, the excessive expression of HOXB8 reduced the growth suppression in SW48 cells caused by cetuximab by triggering the STAT3 signaling pathway. Conclusively, we conclude that HOXB8 has played an essential role in cetuximab-resistant mCRC and that treating HOXB8 specifically may be a useful treatment approach for certain cetuximab-resistant mCRC patients.
Key Molecule: Signal transducer and activator of transcription 3 (STAT3) [30]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation STAT3 signaling pathway Activation hsa04550
In Vitro Model HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 Western blot assay
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description By comparing drug-sensitive cell lines (SW48) with drug-resistant cell lines (HCT116, CACO2), we discovered that HOXB8 was substantially expressed in cetuximab-resistant cell lines, and furthermore, in drug-resistant cell lines (HCT116, CACO2), HOXB8 knockdown increased the cytotoxicity of cetuximab via blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Conversely, the excessive expression of HOXB8 reduced the growth suppression in SW48 cells caused by cetuximab by triggering the STAT3 signaling pathway. Conclusively, we conclude that HOXB8 has played an essential role in cetuximab-resistant mCRC and that treating HOXB8 specifically may be a useful treatment approach for certain cetuximab-resistant mCRC patients.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-7 [31]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description microRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Epidermal growth factor receptor (EGFR) [31]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description microRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation.
Key Molecule: RAF proto-oncogene serine/threonine-protein kinase (RAF1) [31]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description microRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation.
Key Molecule: Homeobox protein Hox-B8 (HOXB8) [30]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation STAT3 signaling pathway Activation hsa04550
In Vitro Model SW48 cells Colon Homo sapiens (Human) CVCL_1724
Experiment for
Molecule Alteration		 Western blot assay
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description By comparing drug-sensitive cell lines (SW48) with drug-resistant cell lines (HCT116, CACO2), we discovered that HOXB8 was substantially expressed in cetuximab-resistant cell lines, and furthermore, in drug-resistant cell lines (HCT116, CACO2), HOXB8 knockdown increased the cytotoxicity of cetuximab via blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Conversely, the excessive expression of HOXB8 reduced the growth suppression in SW48 cells caused by cetuximab by triggering the STAT3 signaling pathway. Conclusively, we conclude that HOXB8 has played an essential role in cetuximab-resistant mCRC and that treating HOXB8 specifically may be a useful treatment approach for certain cetuximab-resistant mCRC patients.
Key Molecule: Signal transducer and activator of transcription 3 (STAT3) [30]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cetuximab
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation STAT3 signaling pathway Activation hsa04550
In Vitro Model SW48 cells Colon Homo sapiens (Human) CVCL_1724
Experiment for
Molecule Alteration		 Western blot assay
Experiment for
Drug Resistance		 MTT assay; Colony formation assay
Mechanism Description By comparing drug-sensitive cell lines (SW48) with drug-resistant cell lines (HCT116, CACO2), we discovered that HOXB8 was substantially expressed in cetuximab-resistant cell lines, and furthermore, in drug-resistant cell lines (HCT116, CACO2), HOXB8 knockdown increased the cytotoxicity of cetuximab via blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Conversely, the excessive expression of HOXB8 reduced the growth suppression in SW48 cells caused by cetuximab by triggering the STAT3 signaling pathway. Conclusively, we conclude that HOXB8 has played an essential role in cetuximab-resistant mCRC and that treating HOXB8 specifically may be a useful treatment approach for certain cetuximab-resistant mCRC patients.
Chloroquine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: . [32]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Chloroquine
 Drug Info 
Molecule Alteration .
.
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Wnt/beta-catenin Signalling Pathway Regulation N.A.
In Vitro Model HCT8 cells Colon Homo sapiens (Human) CVCL_2478
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description The results showed that Huaier can regulate autophagy, inhibit the Wnt/-catenin signalling pathway and reverse the drug resistance of OXA-resistant CRC cells.
Cisplatin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-1271 [33]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description miR-1271 enhances the sensitivity of colorectal cancer cells to cisplatin via downregulating mTOP.
Key Molecule: hsa-mir-199a [34]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Regulation N.A.
In Vitro Model ALDHA1+ CCSCs cells Colon Homo sapiens (Human) N.A.
ALDHA1 cells Colon Homo sapiens (Human) N.A.
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Flow cytometry assay; MTT assay
Mechanism Description Upregulation of miR199a/b contributes to cisplatin resistance via Wnt/beta-catenin-ABCG2 signaling pathway in ALDHA1+ colorectal cancer stem cells. Gsk3beta was the direct target of miR199a/b, miR199a/b regulates Wnt/beta-catenin pathway by targeting Gsk3beta in ALDHA1+ CCSCs.
Key Molecule: hsa-mir-199b [34]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Regulation N.A.
In Vitro Model ALDHA1+ CCSCs cells Colon Homo sapiens (Human) N.A.
ALDHA1 cells Colon Homo sapiens (Human) N.A.
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Flow cytometry assay; MTT assay
Mechanism Description Upregulation of miR199a/b contributes to cisplatin resistance via Wnt/beta-catenin-ABCG2 signaling pathway in ALDHA1+ colorectal cancer stem cells. Gsk3beta was the direct target of miR199a/b, miR199a/b regulates Wnt/beta-catenin pathway by targeting Gsk3beta in ALDHA1+ CCSCs.
Key Molecule: Pvt1 oncogene (PVT1) [35]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
Intrinsic apoptotic signaling pathway Inhibition hsa04210
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
RkO cells Colon Homo sapiens (Human) CVCL_0504
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; TUNEL assay; Flow cytometry assay
Mechanism Description PVT1 involved in cisplatin resistance of CRC cells via upregulation of drug resistance-associated molecules, including multidrug resistance 1 (MDR1) and multidrug resistance protein 1 (MRP1), by blocking the intrinsic apoptotic pathway.
Key Molecule: hsa-mir-153 [36]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
DLD1 cells Colon Homo sapiens (Human) CVCL_0248
SW620 cells Colon Homo sapiens (Human) CVCL_0547
CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
SW48 cells Colon Homo sapiens (Human) CVCL_1724
COLO205 cells Colon Homo sapiens (Human) CVCL_F402
In Vivo Model SCID nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTS assay; Soft agar colony forming ability assay; Flow cytometry assay
Mechanism Description miR-153 promoted invasiveness indirectly by inducing MMP9 production, whereas drug resistance was mediated directly by inhibiting the Forkhead transcription factor FOXO3a.
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [35]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
Intrinsic apoptotic signaling pathway Inhibition hsa04210
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
RkO cells Colon Homo sapiens (Human) CVCL_0504
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; TUNEL assay; Flow cytometry assay
Mechanism Description PVT1 involved in cisplatin resistance of CRC cells via upregulation of drug resistance-associated molecules, including multidrug resistance 1 (MDR1) and multidrug resistance protein 1 (MRP1), by blocking the intrinsic apoptotic pathway.
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Key Molecule: microRNA-137 (miR-137) [37]
Metabolic Type Glutamine metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
LOVO cells Colon Homo sapiens (Human) CVCL_0399
SW-480 cells Colon Homo sapiens (Human) CVCL_0546
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Using a microRNA (miRNA) microArray assay, miR-137, a tumor suppressor in colon cancer, was significantly induced by curcumin treatments in CRC cells. Bioinformatics analysis and a luciferase assay illustrated miR-137 directly targeted the 3' UTR of GLS mRNA. Rescue experiments demonstrated that miR-137-induced cisplatin sensitization was through targeting of GLS. Finally, curcumin treatment overcame cisplatin resistance through miR-137-mediated glutamine inhibition.
Key Molecule: YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) [38]
Metabolic Type Glutamine metabolism
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
LOVO cells Colon Homo sapiens (Human) CVCL_0399
SW-480 cells Colon Homo sapiens (Human) CVCL_0546
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Overexpression of YTHDF1 decreased the cisplatin sensitivity of colon cancer cells. From the established cisplatin-resistant CRC cell line (LoVo CDDP R), we detected that YTHDF1 was significantly upregulated in cisplatin-resistant CRC cells. Intriguingly, RNA sequencing (RNA-seq) results revealed that glutamine metabolism enzymes were clearly upregulated in LoVo CDDP R cells. Glutamine uptake, that is, glutaminase (GLS) activity, was upregulated in LoVo CDDP R cells. Furthermore, bioinformatics analysis indicated that the 3' UTR of GLS1 contained a putative binding motif of YTHDF1, and an interaction was further validated by a protein-RNA interaction assay (RNA immunoprecipitation [RIP]).
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase mTOR (mTOR) [33]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
Experiment for
Molecule Alteration		 Western blot analysis; RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description miR-1271 enhances the sensitivity of colorectal cancer cells to cisplatin via downregulating mTOP.
Key Molecule: Glycogen synthase kinase-3 beta (GSK3B) [34]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Regulation N.A.
In Vitro Model ALDHA1+ CCSCs cells Colon Homo sapiens (Human) N.A.
ALDHA1 cells Colon Homo sapiens (Human) N.A.
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Immunohistochemistry; Luciferase reporter assay
Experiment for
Drug Resistance		 Flow cytometry assay; MTT assay
Mechanism Description Upregulation of miR199a/b contributes to cisplatin resistance via Wnt/beta-catenin-ABCG2 signaling pathway in ALDHA1+ colorectal cancer stem cells. Gsk3beta was the direct target of miR199a/b, miR199a/b regulates Wnt/beta-catenin pathway by targeting Gsk3beta in ALDHA1+ CCSCs.
Key Molecule: Forkhead box protein O3 (FOXO3) [36]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell proliferation Activation hsa05200
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
DLD1 cells Colon Homo sapiens (Human) CVCL_0248
SW620 cells Colon Homo sapiens (Human) CVCL_0547
CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
SW48 cells Colon Homo sapiens (Human) CVCL_1724
COLO205 cells Colon Homo sapiens (Human) CVCL_F402
In Vivo Model SCID nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay; Soft agar colony forming ability assay; Flow cytometry assay
Mechanism Description miR-153 promoted invasiveness indirectly by inducing MMP9 production, whereas drug resistance was mediated directly by inhibiting the Forkhead transcription factor FOXO3a.
Key Molecule: Non-coding RNA activated by DNA damage (NORAD) [39]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation miR-106a-5p/Cyclin D1 signalling pathway Regulation N.A.
In Vitro Model HT-29 cells Colon Homo sapiens (Human) CVCL_0320
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Clonogenic assay
Mechanism Description In the established cisplatin resistant cell line, NORAD was upregulated and miR-106a-5p was downregulated. Furthermore, we disclosed miR-106a-5p directly targeted 3'UTR of CCND1, which is an important cell cycle regulator and is frequently overexpressed in human cancers. Rescue experiments showed restoration of CCND1 in miR-106a-5p-overexpressing CRC cells successfully recovered cisplatin resistance. Finally, restoration of miR-106a-5p in NORAD-overexpressing CRC cells re-sensitized cisplatin resistance by targeting CCND1. Summarily, this study uncovered a NORAD-promoted cisplatin resistance through modulating the miR-106a-5p-CCND1 axis.
Key Molecule: hsa-miR-106a-5p [39]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation miR-106a-5p/Cyclin D1 signalling pathway Regulation N.A.
In Vitro Model HT-29 cells Colon Homo sapiens (Human) CVCL_0320
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Clonogenic assay
Mechanism Description In the established cisplatin resistant cell line, NORAD was upregulated and miR-106a-5p was downregulated. Furthermore, we disclosed miR-106a-5p directly targeted 3'UTR of CCND1, which is an important cell cycle regulator and is frequently overexpressed in human cancers. Rescue experiments showed restoration of CCND1 in miR-106a-5p-overexpressing CRC cells successfully recovered cisplatin resistance. Finally, restoration of miR-106a-5p in NORAD-overexpressing CRC cells re-sensitized cisplatin resistance by targeting CCND1. Summarily, this study uncovered a NORAD-promoted cisplatin resistance through modulating the miR-106a-5p-CCND1 axis.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-148a [40]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Beta-catenin signaling pathway Inhibition hsa04520
Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell viability Inhibition hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
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-148a suppressed expression of stem cell markers, inhibited sphere formation, invasion and migration, induced apoptosis, and reduced chemo-resistance in cisplatin-resistant SW480 cells while suppressing WNT10b expression and beta-catenin signaling activities.
Key Molecule: hsa-mir-20a [41]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
ROS/ASk1/JNk signaling pathway Activation hsa04071
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
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		 MTT assay; Flow cytometry assay
Mechanism Description Knockdown of miR-20a enhanced sensitivity of colorectal cancer cells to cisplatin through the ROS/ASk1/JNk pathway.
Key Molecule: hsa-mir-497 [42]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
MEK/ERK signaling pathway Inhibition hsa04011
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW620 cells Colon Homo sapiens (Human) CVCL_0547
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
COLO 205 cells Colon Homo sapiens (Human) CVCL_0218
HCT28 cells Colon Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description IGF1-R has an important role in mediating activation of the PI3k/Akt pathway, miR-497 inhibits PI3k/Akt signalling. Down-regulation of miR-497 is an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Protein Wnt-10b (WNT10B) [40]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Beta-catenin signaling pathway Inhibition hsa04520
Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell viability Inhibition hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
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-148a suppressed expression of stem cell markers, inhibited sphere formation, invasion and migration, induced apoptosis, and reduced chemo-resistance in cisplatin-resistant SW480 cells while suppressing WNT10b expression and beta-catenin signaling activities.
Key Molecule: Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) [41]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Phosphorylation
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
ROS/ASk1/JNk signaling pathway Activation hsa04071
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
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		 MTT assay; Flow cytometry assay
Mechanism Description Knockdown of miR-20a enhanced sensitivity of colorectal cancer cells to cisplatin through the ROS/ASk1/JNk pathway.
Key Molecule: Insulin-like growth factor 1 receptor (IGF1R) [42]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
MEK/ERK signaling pathway Inhibition hsa04011
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW620 cells Colon Homo sapiens (Human) CVCL_0547
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
COLO 205 cells Colon Homo sapiens (Human) CVCL_0218
HCT28 cells Colon Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description IGF1-R has an important role in mediating activation of the PI3k/Akt pathway, miR-497 inhibits PI3k/Akt signalling. Down-regulation of miR-497 is an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC.
Colchicine
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [43]
Sensitive Disease Colorectal carcinoma [ICD-11: 2B91.3]
Sensitive Drug Colchicine
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
NIH-G185 cells Ovary Homo sapiens (Human) CVCL_L991
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.
Dabrafenib/Trametinib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [44]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Dabrafenib/Trametinib
 Drug Info 
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.55  Å
PDB: 4E26
Mutant Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 4G9R
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.53
TM score: 0.95765
Amino acid change:
V600E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
420
|
M
M
D
D
R
R
G
G
S
S
H
H
H
H
H
H
H
H
H
H
430
|
H
H
G
G
S
S
E
E
D
D
R
R
N
N
R
R
M
M
K
K
440
|
T
T
L
L
G
G
R
R
R
R
D
D
S
S
S
S
D
D
D
D
450
|
W
W
E
E
I
I
P
P
D
D
G
G
Q
Q
I
I
T
T
V
V
460
|
G
G
Q
Q
R
R
I
I
G
G
S
S
G
G
S
S
F
F
G
G
470
|
T
T
V
V
Y
Y
K
K
G
G
K
K
W
W
H
H
G
G
D
D
480
|
V
V
A
A
V
V
K
K
M
M
L
L
N
N
V
V
T
T
A
A
490
|
P
P
T
T
P
P
Q
Q
Q
Q
L
L
Q
Q
A
A
F
F
K
K
500
|
N
N
E
E
V
V
G
G
V
V
L
L
R
R
K
K
T
T
R
R
510
|
H
H
V
V
N
N
I
I
L
L
L
L
F
F
M
M
G
G
Y
Y
520
|
S
S
T
T
K
K
P
P
Q
Q
L
L
A
A
I
I
V
V
T
T
530
|
Q
Q
W
W
C
C
E
E
G
G
S
S
S
S
L
L
Y
Y
H
H
540
|
H
H
L
L
H
H
I
I
I
I
E
E
T
T
K
K
F
F
E
E
550
|
M
M
I
I
K
K
L
L
I
I
D
D
I
I
A
A
R
R
Q
Q
560
|
T
T
A
A
Q
Q
G
G
M
M
D
D
Y
Y
L
L
H
H
A
A
570
|
K
K
S
S
I
I
I
I
H
H
R
R
D
D
L
L
K
K
S
S
580
|
N
N
N
N
I
I
F
F
L
L
H
H
E
E
D
D
L
L
T
T
590
|
V
V
K
K
I
I
G
G
D
D
F
F
G
G
L
L
A
A
T
T
600
|
V
E
K
K
S
S
R
R
W
W
S
S
G
G
S
S
H
H
Q
Q
610
|
F
F
E
E
Q
Q
L
L
S
S
G
G
S
S
I
I
L
L
W
W
620
|
M
M
A
A
P
P
E
E
V
V
I
I
R
R
M
M
Q
Q
D
D
630
|
K
K
N
N
P
P
Y
Y
S
S
F
F
Q
Q
S
S
D
D
V
V
640
|
Y
Y
A
A
F
F
G
G
I
I
V
V
L
L
Y
Y
E
E
L
L
650
|
M
M
T
T
G
G
Q
Q
L
L
P
P
Y
Y
S
S
N
N
I
I
660
|
N
N
N
N
R
R
D
D
Q
Q
I
I
I
I
F
F
M
M
V
V
670
|
G
G
R
R
G
G
Y
Y
L
L
S
S
P
P
D
D
L
L
S
S
680
|
K
K
V
V
R
R
S
S
N
N
C
C
P
P
K
K
A
A
M
M
690
|
K
K
R
R
L
L
M
M
A
A
E
E
C
C
L
L
K
K
K
K
700
|
K
K
R
R
D
D
E
E
R
R
P
P
L
L
F
F
P
P
Q
Q
710
|
I
I
L
L
A
A
S
S
I
I
E
E
L
L
L
L
A
A
R
R
720
|
S
S
L
L
P
P
K
K
I
I
H
H
R
R
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [45]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Dabrafenib/Trametinib
 Drug Info 
Molecule Alteration Missense mutation
p.V600X (c.1798_1800)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Colorectum N.A.
In Vivo Model Patient-Derived xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Reverse-phase protein array (RPPA) analysis; Targeted next-generation sequencing (NGS) assay
Experiment for
Drug Resistance		 Immunohistochemistry assay
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [45]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Dabrafenib/Trametinib
 Drug Info 
Molecule Alteration Missense mutation
p.V600X (c.1798_1799)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Colorectum N.A.
In Vivo Model Patient-Derived xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Reverse-phase protein array (RPPA) analysis; Targeted next-generation sequencing (NGS) assay
Experiment for
Drug Resistance		 Immunohistochemistry assay
Docetaxel
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [46]
Resistant Disease Colorectal carcinoma [ICD-11: 2B91.3]
Resistant Drug Docetaxel
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LOVO cells Colon Homo sapiens (Human) CVCL_0399
In Vivo Model Athymic nu/nu female mice xenograft model Mus musculus
Experiment for
Drug Resistance		 MTS assay
Mechanism Description In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.
Doxorubicin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Glycogen synthase kinase-3 beta (GSK3B) [47]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Regulation N.A.
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW480/ADM cells Colon Homo sapiens (Human) CVCL_0546
Experiment for
Molecule Alteration		 Dual luciferase gene reporter assay
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay; EdU staining
Mechanism Description miR224 up-regulation is associated with ADM resistance of CRC cells. Suppression of miR224 expression up-regulated GSk-3beta expression, inhibited Wnt/beta-catenin signal pathway activity and Survivin expression, as well as reduced ADM resistance of CRC SW480 cells.
Key Molecule: hsa-mir-224 [47]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Regulation N.A.
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW480/ADM cells Colon Homo sapiens (Human) CVCL_0546
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay; EdU staining
Mechanism Description miR224 up-regulation is associated with ADM resistance of CRC cells. Suppression of miR224 expression up-regulated GSk-3beta expression, inhibited Wnt/beta-catenin signal pathway activity and Survivin expression, as well as reduced ADM resistance of CRC SW480 cells.
Key Molecule: hsa-miR-297 [8]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
HCT-116 cells Colon Homo sapiens (Human) CVCL_0291
Experiment for
Molecule Alteration		 miRNA Microarray Analysis; qRT-PCR; Luciferase Activity Assay; Western Blot; Semi-Quantitative RT-PCR
Experiment for
Drug Resistance		 Caspase-3 Activity Assay; In Vitro Drug Sensitivity Assay; Flow Cytometric
Mechanism Description Taken together, our findings suggest that miR-1915 could play a role in the development of MDR in colorectal carcinoma cells at least in part by modulation of apoptosis via targeting Bcl-2.
Key Molecule: XIST [11]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
LOVO cells Colon Homo sapiens (Human) CVCL_0399
In Vivo Model Colorectal cancer patients; Nude mouse xenograft model Homo sapiens
Experiment for
Molecule Alteration		 RT-qPCR; Western blot; Luciferase reporter assay
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description XIST expression was upregulated and miR-124 expression was downregulated in DOX-resistant CRC tissues and cells. Knockdown of XIST inhibited DOX resistance of CRC cells, as evidenced by the reduced IC50 value of DOX, decreased P-gp and GST-pi levels and enhanced apoptosis in XIST-silenced DOX-resistant CRC cells. Additionally, XIST positively regulated SGK1 expression by interacting with miR-124 in DOX-resistant CRC cells. miR-124 suppression strikingly reversed XIST knockdown-mediated repression on DOX resistance in DOX-resistant CRC cells.
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: SLC25A25 antisense RNA 1 (SLC25A25-AS1) [48]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
ERK/p38 signaling pathway Inhibition hsa04210
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description SLC25A25-AS1 overexpression significantly inhibited proliferation and colony formation in colorectal cancer cell lines, and downregulation of SLC25A25-AS1 obviously (+) chemoresistance and promoted EMT process in vitro associated with Erk and p38 signaling pathway activation. Therefore, SLC25A25-AS1 was determined to play a tumor suppressive role in CRC.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Cytochrome P450 family 3 subfamily A member1 (CYP3A4) [49]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
Experiment for
Molecule Alteration		 CYP450-Glo CYP 3A4 assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description In this study, resveratrol was a significant inhibitor of CYP3A4 enzyme activity with IC50 value 9.32 ( M). Moreover, the CYP3A4 mRNA levels were reduced after treatment with resveratrol 0.03-fold of the control levels with high significance (p < 0.001).
Key Molecule: Glutathione S-transferase (GST) [49]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
Experiment for
Molecule Alteration		 Glutathione-S-transferase assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The Glutathione-S-transferases (GSTs) are a multigene family of dimeric proteins which play a central role in the detoxification of electrophilic xenobiotics and catalyze their conjugation with GSH to electrophilic metabolites, thus rendering them more water soluble. GSTs protect cells from cytotoxic and carcinogenic chemicals. GST activity was decreased by resveratrol in a dose dependent manner. IC50 value was 30.73 M. This results were confirmed by RT-PCR data, where the tested samples changed the GST mRNA level by 0.79-fold (p < 0.01) of control level.
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-29a-3p [50]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K/AKT pathway Regulation N.A.
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Here, the functional effects of miR-29a in chemo-resistant colon cancer cells is scrutinized. The effect of doxorubicin (DOX) on cell proliferation after miR-29a transfection has been evaluated using MTT assay in HT29 and HT29/DOX cells. Rhodamine123 (Rh123) assay is used to identify the activity of common drug efflux through membrane transporters P-glycoprotein (P-gp). P-gp and PTEN mRNA/protein expression levels were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Flow cytometry was employed to the investigation of apoptosis. ANOVA followed by Bonferroni's and Sidak's tests were used to compare the data from different groups. Thus, it was shown that miRNA-29a overexpression considerably inhibited the HT29/DOX viability. miR-29a significantly down-regulated P-gp expression and activity in HT29/DOX cells and declined drug resistance through elevation of intracellular DOX. Furthermore, upon miRNA-29a transfection, PTEN expression could be restored in resistant cells. These results have indicated that miR-29a target PTEN ultimately P-gp, which is downstream of PTEN, inhibit drug resistance, proliferation, and apoptosis through PI3K/Akt pathway. As a result, miR-29a overexpression is led to enhance the sensitivity of HT29/DOX cells to DOX-treatment by targeting P-gp. MiR-29a might proffer a novel promising candidate for colon cancer therapeutics during chemotherapy.
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [51]
Sensitive Disease Colorectal carcinoma [ICD-11: 2B91.3]
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
In Vitro Model HCT8 cells Colon Homo sapiens (Human) CVCL_2478
CT26 cells Colon Mus musculus (Mouse) CVCL_7254
Salmonella enterica serovar Typhimurium SL1344 216597
Salmonella enterica serovar Typhimurium SL1344 detaSipA 216597
Salmonella enterica serovar Typhimurium SL1344 detaSipB 216597
Salmonella enterica serovar Typhimurium SL1344 detaSipC 216597
Salmonella enterica serovar Typhimurium SL1344 detaSopB 216597
In Vivo Model BALB/c mice xenograft model Mus musculus
Experiment for
Drug Resistance		 MTS assay
Mechanism Description Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin).
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [43]
Sensitive Disease Colorectal carcinoma [ICD-11: 2B91.3]
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
HCT-8 cells Colon Homo sapiens (Human) CVCL_2478
NIH-G185 cells Ovary Homo sapiens (Human) CVCL_L991
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.
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [49]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model CaCo2 cells Colon Homo sapiens (Human) CVCL_0025
Experiment for
Molecule Alteration		 Efflux of rhodamine123 assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Resveratrol can restore the sensitivity of Caco-2 and CEM/ADR5000 cell lines to doxorubicin, through enhancing significantly doxorubicin cytotoxicity. ABC-transporter inhibitors, classified according to their action on ABC-transporters proteins into: 1. Function inhibitors, 2. Expression inhibitors, and 3. Functional and expression inhibitors, which have an ideal characters of ABC-transporters inhibitors. Our results indicate that resveratrol falls into the class 3 inhibitors.
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: F-box/WD repeat-containing protein 7 (FBXW7) [52]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
miR223/FBXW7 signaling pathway Regulation N.A.
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW620 cells Colon Homo sapiens (Human) CVCL_0547
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of CRC cells to doxorubicin, while suppression of miR-223 had the opposite effect.
Key Molecule: hsa-mir-223 [52]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
miR223/FBXW7 signaling pathway Regulation N.A.
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
SW620 cells Colon Homo sapiens (Human) CVCL_0547
LOVO cells Colon Homo sapiens (Human) CVCL_0399
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of CRC cells to doxorubicin, while suppression of miR-223 had the opposite effect.
Entrectinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Tropomyosin-related kinase A (TrkA) [53]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Entrectinib
 Drug Info 
Molecule Alteration Missense mutation
p.G595R (c.1783G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 5H3Q
Mutant Type Structure Method: X-ray diffraction Resolution: 2.09  Å
PDB: 8J5X
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.34
TM score: 0.93325
Amino acid change:
G595R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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G
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480
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490
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D
500
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510
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520
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530
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D
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540
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550
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560
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570
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580
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590
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M
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G
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D
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600
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610
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620
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630
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640
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650
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660
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F
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670
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680
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690
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700
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710
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720
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730
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740
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750
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760
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770
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780
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790
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G
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model KM-12 cells Colon Homo sapiens (Human) CVCL_1331
In Vivo Model NOD-SCID mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 ddPCR; Kinase domain alignment assay
Key Molecule: Tropomyosin-related kinase A (TrkA) [53]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Entrectinib
 Drug Info 
Molecule Alteration Missense mutation
p.G667C (c.1999G>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model KM-12 cells Colon Homo sapiens (Human) CVCL_1331
In Vivo Model NOD-SCID mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 ddPCR; Kinase domain alignment assay
Fentanyl
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: BRAF-activated non-protein coding RNA (BANCR) [54]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fentanyl
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
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		 Transwell assay
Mechanism Description Fentanyl inhibits the invasion and migration of colorectal cancer cells via inhibiting the negative regulation of Ets-1 on BANCR.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Protein C-ets-1 (ETS1) [54]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Resistant Drug Fentanyl
 Drug Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
LOVO cells Colon Homo sapiens (Human) CVCL_0399
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 Transwell assay
Mechanism Description Fentanyl inhibits the invasion and migration of colorectal cancer cells via inhibiting the negative regulation of Ets-1 on BANCR.
Clinical Trial Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
TRAIL
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: BH3-interacting domain death agonist (BID) [5]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Sensitive Drug TRAIL
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Colorectal cancer [ICD-11: 2B91]
The Specified Disease Colorectal cancer
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.45E-74
Fold-change: 1.65E+00
Z-score: 2.47E+01
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation TBID/Mitochondria signaling pathway Activation hsa04217
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
NCI-H508 cells Colon Homo sapiens (Human) CVCL_1564
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
SW948 cells Colon Homo sapiens (Human) CVCL_0632
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; FITC-Annexin V and propidium iodide (PI) assay
Mechanism Description The knockdown of miR20a inhibited the translocation of tBID to the mitochondria, which induced the mitochondrial pathway of apoptosis, the knockdown of miR20a also reversed the resistance of TRAIL in established TRAIL-resistant SW480 cells by tBID-mitochondria pathway.
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