Molecule Information

General Information of the Molecule (ID: Mol00050)
Name
Cellular tumor antigen p53 (TP53) ,Homo sapiens
Synonyms
Antigen NY-CO-13; Phosphoprotein p53; Tumor suppressor p53; P53
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Molecule Type
Protein
Gene Name
TP53
Gene ID
7157
Location
chr17:7661779-7687538[-]
Sequence
MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP
DEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAK
SVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHE
RCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNS
SCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELP
PGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPG
GSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD
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Function
Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2. However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2.
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Uniprot ID
P53_HUMAN
Ensembl ID
ENSG00000141510
HGNC ID
HGNC:11998
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  ADTT: Aberration of the Drug's Therapeutic Target
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
17 drug(s) in total
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Bendamustine hydrochloride
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Chronic lymphocytic leukemia [1]
Resistant Disease Chronic lymphocytic leukemia [ICD-11: 2A82.0]
 Disease Info 
Resistant Drug Bendamustine hydrochloride
 Drug Info 
Molecule Alteration Mutation
.
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Whole exome sequencing assay; Targeted deep sequencing assay; Sanger sequencing assay
Mechanism Description Following exposure to chemoimmunotherapy, the resistant TP53 aberrant clones accumulate and dominate the tumour.
Carboplatin
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: Ovarian cancer [2]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug Carboplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model 3AO cells Ovary Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description LncRNA PVT1 boost the expression of p53 and TIMP 1 to enhance ovarian cancer cells chemosensitivity for carboplatin and docetaxel.
Cisplatin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Bladder cancer [3]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
T24 cells Bladder Homo sapiens (Human) CVCL_0554
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
Experiment for
Molecule Alteration		 Western blot analysis; qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description Upregulated HIF1A-AS2 hampers the p53 family proteins dependent apoptotic pathway to promote Cis resistance in bladder cancer.
Disease Class: Nasopharyngeal carcinoma [4]
Resistant Disease Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
 Disease Info 
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
p53 signaling pathway Inhibition hsa04115
In Vitro Model CNE1 cells Throat Homo sapiens (Human) CVCL_6888
CNE-2 cells Nasopharynx Homo sapiens (Human) CVCL_6888
TW03 cells Nasopharynx Homo sapiens (Human) CVCL_6010
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description In the TW03/DDP cells, the expression levels of miR 125a and miR 125b were upregulated, and this caused downregulation of p53. Ectopic expression of these miRNAs in the TW03 cell model sensitized TW03 to cisplatin by decreasing the protein expression levels of p53, whereas ectopic expression in the antisense oligos of these microRNAs demonstrated the opposite effect. In addition, the present demonstrated that the cisplatin induced expression of miR 125a and miR 125b inhibited cisplatin induced apoptosis in the TW03 cells by decreasing the protein expression levels of p53. Taken together, the present study revealed for the first time, to the best of our knowledge, that induction of the expression of miR 125a and miR 125b by treatment with cisplatin resulted in resistance to the cisplatin drug in the NPC cells.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Non-small cell lung cancer [5]
Sensitive Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
p53/p66shc signaling pathway Activation hsa04115
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
A549/DDP cells Lung Homo sapiens (Human) CVCL_0023
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometric analysis
Mechanism Description Downregulated long non-coding RNA TRPM2-AS inhibits cisplatin resistance of non-small cell lung cancer cells via activation of p53- p66shc pathway.
Disease Class: Lung cancer [6]
Sensitive Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
Wnt/Beta-catenin signaling pathway Inhibition hsa04310
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description Down-regulation of Meg3 enhances cisplatin resistance of lung cancer cells through activation of the WNT/beta-catenin signaling pathway.The present study detected that the expression levels of Meg3 were significantly lower in cisplatin-resistant A549/DDP lung cancer cells, compared with those in parental A549 cells. The results of the present study also demonstrated that the Meg3-mediated chemosensitivity enhancement was associated with the induction of cell-cycle arrest and increased apoptosis, through regulation of p53, beta-catenin and survivin, which is a target gene of the WNT/beta-catenin signaling pathway.
Docetaxel
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast cancer bone metastasis [7]
Resistant Disease Breast cancer bone metastasis [ICD-11: 2E03.1]
 Disease Info 
Resistant Drug Docetaxel
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 Flow cytometric
Mechanism Description Interleukin-6 (IL-6), a pro-inflammatory cytokine produced in the tumor microenvironment by stromal cells, fibroblasts, and cancer cells. Binding of IL-6 to its receptor IL-6R on the cell membrane activates Janus Kinase 2 (JAK2) kinases. Activated JAK2 mediates phosphorylation, dimerization, and nuclear translocation of Signal Transducer and Activator of Transcription 3 (STAT3). STAT3 signaling mediates the expression of various genes, including p53, Bcl-2, MRP1, and ABCG2. Bcl-2 and p53 are associated with regulation of apoptosis while overexpression of drug transporters MRP1, ABCG2 has been shown to mediate efflux of drugs from cancer cells, thus decreasing intracellular drug concentration leading to drug-resistance.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: Ovarian cancer [2]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug Docetaxel
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model 3AO cells Ovary Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description LncRNA PVT1 boost the expression of p53 and TIMP 1 to enhance ovarian cancer cells chemosensitivity for carboplatin and docetaxel.
Doxorubicin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Ewing sarcoma [8]
Resistant Disease Ewing sarcoma [ICD-11: 2B52.0]
 Disease Info 
Resistant Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
miR125b-p53/BAKT signaling pathway Activation hsa05206
In Vitro Model RD-ES cells Bones Homo sapiens (Human) CVCL_2169
Sk-ES cells Bones Homo sapiens (Human) CVCL_0627
Sk-N-MC cells Bones Homo sapiens (Human) CVCL_0530
TC-71 cells Bones Homo sapiens (Human) CVCL_2213
VH-64 cells Bones Homo sapiens (Human) CVCL_9672
WE-68 cells Bones Homo sapiens (Human) CVCL_9717
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Celltiter-glo luminescent cell viability assay
Mechanism Description miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Hepatocellular carcinoma [9]
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
NF-kappaB p65/p53 signaling pathway Regulation hsa04064
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
HCCLM3 cells Liver Homo sapiens (Human) CVCL_6832
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
MHCC97-H cells Liver Homo sapiens (Human) CVCL_4972
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 LncRNA 00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity, inhibiting the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC.
Disease Class: Glioma [10]
Sensitive Disease Glioma [ICD-11: 2A00.1]
 Disease Info 
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT signaling pathway Inhibition hsa04151
Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U251 cells Brain Homo sapiens (Human) CVCL_0021
U87-MG cells Brain Homo sapiens (Human) CVCL_0022
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay; Flow cytometry assay
Mechanism Description microRNA-127 silencing significantly affects cell growth and increases the sensitivity to adriamycin. microRNA-127 silencing arrests the cell cycle, potentiates adriamycin-induced apoptosis, and increases cellular Rh-123 uptake. microRNA-127 silencing down-regulates MDR1, MRP1, Runx2, Bcl-2, Survivin and ErbB4 expression while up-regulates p53 expression. microRNA-127 silencing inhibits AkT phosphorylation.
Etoposide
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Ewing sarcoma [8]
Resistant Disease Ewing sarcoma [ICD-11: 2B52.0]
 Disease Info 
Resistant Drug Etoposide
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
miR125b-p53/BAKT signaling pathway Activation hsa05206
In Vitro Model RD-ES cells Bones Homo sapiens (Human) CVCL_2169
Sk-ES cells Bones Homo sapiens (Human) CVCL_0627
Sk-N-MC cells Bones Homo sapiens (Human) CVCL_0530
TC-71 cells Bones Homo sapiens (Human) CVCL_2213
VH-64 cells Bones Homo sapiens (Human) CVCL_9672
WE-68 cells Bones Homo sapiens (Human) CVCL_9717
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Celltiter-glo luminescent cell viability assay
Mechanism Description miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.
Fludarabine
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Chronic lymphocytic leukemia [11]
Resistant Disease Chronic lymphocytic leukemia [ICD-11: 2A82.0]
 Disease Info 
Resistant Drug Fludarabine
 Drug Info 
Molecule Alteration Mutation
.
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation NF-kB signaling pathway Inhibition hsa04218
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Mechanism Description Genes belonging to the DNA damage response and cell cycle control (TP53, ATM, POT1, BIRC3) happen to be more frequently mutated in uCLL cases. However, DNA-damaging chemotherapy results in the development of chemo-resistance in most of the cases, which has been initially attributed to the selection of driver mutations affecting genes of the DNA-damage response pathways, such as TP53 and ATM.
Fluorouracil
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Hepatocellular carcinoma [9]
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
NF-kappaB p65/p53 signaling pathway Regulation hsa04064
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
HCCLM3 cells Liver Homo sapiens (Human) CVCL_6832
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
MHCC97-H cells Liver Homo sapiens (Human) CVCL_4972
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 LncRNA 00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity, inhibiting the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC.
Gefitinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Lung cancer [12]
Resistant Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Resistant Drug Gefitinib
 Drug Info 
Molecule Alteration Missense mutation
p.Y163C
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation AXLK signaling pathway Activation hsa01521
In Vitro Model Plasma Blood Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Circulating-free DNA assay; Whole exome sequencing assay
Mechanism Description Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance.
IFN-alpha
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Hepatocellular carcinoma [9]
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Sensitive Drug IFN-alpha
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
NF-kappaB p65/p53 signaling pathway Regulation hsa04064
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
HCCLM3 cells Liver Homo sapiens (Human) CVCL_6832
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
MHCC97-H cells Liver Homo sapiens (Human) CVCL_4972
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 LncRNA 00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity, inhibiting the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC.
Leflunomide
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Rheumatoid arthritis [13]
Resistant Disease Rheumatoid arthritis [ICD-11: FA20.0]
 Disease Info 
Resistant Drug Leflunomide
 Drug Info 
Molecule Alteration Mutation
p.P151S+p.R175H+p.G245C+p.R282W
Experimental Note Identified from the Human Clinical Data
Mechanism Description The wild-type p53 tumor suppressor (p53) is overexpressed in response to DNA damage and inflammation in RA fibroblast-like synoviocytes (FLS), which are highly specialized mesenchymal cells located in the internal lining of the synovium and are involved in the pathogenesis and progression of RA. In line with the effects of p53 gain-of-function mutation in tumor progression, mutation-mediated gain-of-function of p53 may contribute to the invasiveness and apoptosis-resistant feature of FLS in RA and the increased expression of cartilage degradative proteases, leading to degeneration of cartilage and bone. Gene knockout or gene transfer studies using a collagen-II-induced arthritis (CIA) model have established the crucial role of p53 in RA that provides a basis for additional research to fully characterize the clinical implications of p53 somatic mutations in drug-resistant RA.
Methotrexate
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Rheumatoid arthritis [13]
Resistant Disease Rheumatoid arthritis [ICD-11: FA20.0]
 Disease Info 
Resistant Drug Methotrexate
 Drug Info 
Molecule Alteration Mutation
p.P151S+p.R175H+p.G245C+p.R282W
Experimental Note Identified from the Human Clinical Data
Mechanism Description The wild-type p53 tumor suppressor (p53) is overexpressed in response to DNA damage and inflammation in RA fibroblast-like synoviocytes (FLS), which are highly specialized mesenchymal cells located in the internal lining of the synovium and are involved in the pathogenesis and progression of RA. In line with the effects of p53 gain-of-function mutation in tumor progression, mutation-mediated gain-of-function of p53 may contribute to the invasiveness and apoptosis-resistant feature of FLS in RA and the increased expression of cartilage degradative proteases, leading to degeneration of cartilage and bone. Gene knockout or gene transfer studies using a collagen-II-induced arthritis (CIA) model have established the crucial role of p53 in RA that provides a basis for additional research to fully characterize the clinical implications of p53 somatic mutations in drug-resistant RA.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Lung cancer [14]
Sensitive Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Sensitive Drug Methotrexate
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
P53/P21/EZH2/E-cad signaling pathway Activation hsa04115
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Transwell assay
Mechanism Description Over expression of miR-200c reduced the resistance of A549/MTX cells to MTX with the mechanism of inducing apoptosis through the P53/P21 pathway.
Paclitaxel
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Lung cancer [15]
Sensitive Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Sensitive Drug Paclitaxel
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
MEG3-P53 signaling pathway Activation hsa04115
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description The downregulation of MEG3 attenuated PTX-induced cytotoxicity, whereas upregulation of MEG3 induced cell death and increased P53 expression.
Ponatinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Chronic myelogenous leukemia [16]
Resistant Disease Chronic myelogenous leukemia [ICD-11: 2A20.3]
 Disease Info 
Resistant Drug Ponatinib
 Drug Info 
Molecule Alteration Missense mutation
p.V216M
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation JAKT2/STAT signaling pathway Activation hsa04030
RAF/KRAS/MEK signaling pathway Activation hsa04010
In Vitro Model HL60 cells Peripheral blood Homo sapiens (Human) CVCL_0002
U937 cells Blood Homo sapiens (Human) CVCL_0007
K562 cells Blood Homo sapiens (Human) CVCL_0004
KCL-22 cells Bone marrow Homo sapiens (Human) CVCL_2091
Sup-B15 cells Bone marrow Homo sapiens (Human) CVCL_0103
HEL cells Blood Homo sapiens (Human) CVCL_0001
HMC-1.2 cells Blood Homo sapiens (Human) CVCL_H205
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay; Sanger Sequencing assay
Mechanism Description Po.tinib led to a decrease of ABL T315I positive transcripts from 47% before po.tinib treatment to 16% at the time of po.tinib resistance in this patient, suggesting that both TP53 and ABL mutations were present in the same clone and that the newly acquired TP53 mutation might have caused po.tinib resistance in this patient.
Rituximab
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Chronic lymphocytic leukemia [1]
Resistant Disease Chronic lymphocytic leukemia [ICD-11: 2A82.0]
 Disease Info 
Resistant Drug Rituximab
 Drug Info 
Molecule Alteration Mutation
.
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Whole exome sequencing assay; Targeted deep sequencing assay; Sanger sequencing assay
Mechanism Description Following exposure to chemoimmunotherapy, the resistant TP53 aberrant clones accumulate and dominate the tumour.
Stanozolol
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Hereditary angioedema [17]
Resistant Disease Hereditary angioedema [ICD-11: 4B05.0]
 Disease Info 
Resistant Drug Stanozolol
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Discovered Using In-vivo Testing Model
In Vivo Model Sprague Dawley male rats model Rattus norvegicus
Experiment for
Molecule Alteration		 Gene expression analysis
Mechanism Description Stanozolol can increases levels of Bax, Bcl-2, P53, caspase 3 and Bax/Bcl-2 ratio. Resistance training, 50 and 100 mg/kg Tribulus terrestris and resistance training along with Tribulus terrestris can decrease the Bax, Bcl-2, P53, caspase 3 and Bax/Bcl-2 ratio in rats exposed to Stanozolol.
Vincristine
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Ewing sarcoma [8]
Resistant Disease Ewing sarcoma [ICD-11: 2B52.0]
 Disease Info 
Resistant Drug Vincristine
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
miR125b-p53/BAKT signaling pathway Activation hsa05206
In Vitro Model RD-ES cells Bones Homo sapiens (Human) CVCL_2169
Sk-ES cells Bones Homo sapiens (Human) CVCL_0627
Sk-N-MC cells Bones Homo sapiens (Human) CVCL_0530
TC-71 cells Bones Homo sapiens (Human) CVCL_2213
VH-64 cells Bones Homo sapiens (Human) CVCL_9672
WE-68 cells Bones Homo sapiens (Human) CVCL_9717
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Celltiter-glo luminescent cell viability assay
Mechanism Description miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.
Clinical Trial Drug(s)
7 drug(s) in total
Click to Show/Hide the Full List of Drugs
Ganetespib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast adenocarcinoma [18]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
Disease Class: Breast adenocarcinoma [18]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Missense mutation
p.L194F (c.580C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
Disease Class: Breast adenocarcinoma [18]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Missense mutation
p.R280K (c.839G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
Disease Class: Solid tumour/cancer [18]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Missense mutation
p.R248Q (c.743G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
Disease Class: Ovarian cancer [18]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Missense mutation
p.S241F (c.722C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
Napabucasin
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Colorectal cancer [19]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Sensitive Drug Napabucasin
 Drug Info 
Molecule Alteration Missense mutation
p.R248Q (c.743G>A)
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation JAKT2/STAT3 signaling pathway Inhibition hsa04030
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
H1299 cells Lung Homo sapiens (Human) CVCL_0060
SW1116 cells Colon Homo sapiens (Human) CVCL_0544
LS1034 cells Colon Homo sapiens (Human) CVCL_1382
SW48 cells Colon Homo sapiens (Human) CVCL_1724
Colo320 cells Colon Homo sapiens (Human) CVCL_1989
SW837 cells Colon Homo sapiens (Human) CVCL_1729
DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
SW1463 cells Rectum Homo sapiens (Human) CVCL_1718
In Vivo Model C57BL/6 mouse model Mus musculus
Experiment for
Molecule Alteration		 BCA protein assay; SDS-PAGE assay
Experiment for
Drug Resistance		 Scratch assay; Transwell migration assay; Fluorescent in situ hybridization assay
Mechanism Description The most common p53 mutant R248Q (mutp53) enhances Stat3 activation by binding to Stat3 and displacing SHP2 in colorectal cancer cells. Reduction of mutp53 genetically or by using the HSP90 inhibitor 17AAG reduces Stat3 signaling and the growth of mutp53-driven tumors.
Selumetinib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Melanoma [20]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Sensitive Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.D259Y (c.775G>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance		 CellTiter-Glo assay; Enzymatic kinase assay
APR-246
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Lung adenocarcinoma [21]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug APR-246
 Drug Info 
Molecule Alteration Missense mutation
p.S241F (c.722C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
DMS456 cells Lung Homo sapiens (Human) CVCL_0B92
In Vivo Model Nude male NMRI mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.S241F (c.722C>T) in gene TP53 cause the sensitivity of APR-246 by aberration of the drug's therapeutic target
Disease Class: Lung adenocarcinoma [21]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug APR-246
 Drug Info 
Molecule Alteration Missense mutation
p.R273L (c.818G>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
DMS456 cells Lung Homo sapiens (Human) CVCL_0B92
In Vivo Model Nude male NMRI mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.R273L (c.818G>T) in gene TP53 cause the sensitivity of APR-246 by aberration of the drug's therapeutic target
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Acute myeloid leukemia [22]
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Sensitive Drug APR-246
 Drug Info 
Molecule Alteration Missense mutation
p.V173M (c.517G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Blood .
Experiment for
Molecule Alteration		 TP53 gene mutation status analysis
Experiment for
Drug Resistance		 Pharmacokinetic Analysis
Mechanism Description The missense mutation p.V173M (c.517G>A) in gene TP53 cause the sensitivity of APR-246 by unusual activation of pro-survival pathway
Seliciclib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Lung adenocarcinoma [23]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Resistant Drug Seliciclib
 Drug Info 
Molecule Alteration Missense mutation
p.P98A (c.292C>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell death detection ELISA assay
Mechanism Description The missense mutation p.P98A (c.292C>G) in gene TP53 cause the resistance of Seliciclib by unusual activation of pro-survival pathway
Disease Class: Lung adenocarcinoma [23]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Resistant Drug Seliciclib
 Drug Info 
Molecule Alteration Missense mutation
p.A159V (c.476C>T)
Experimental Note Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell death detection ELISA assay
Mechanism Description The missense mutation p.A159V (c.476C>T) in gene TP53 cause the resistance of Seliciclib by unusual activation of pro-survival pathway
Disease Class: Lung adenocarcinoma [23]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Resistant Drug Seliciclib
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell death detection ELISA assay
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the resistance of Seliciclib by unusual activation of pro-survival pathway
Disease Class: Lung adenocarcinoma [23]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Resistant Drug Seliciclib
 Drug Info 
Molecule Alteration Missense mutation
p.S215G (c.643A>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell death detection ELISA assay
Mechanism Description The missense mutation p.S215G (c.643A>G) in gene TP53 cause the resistance of Seliciclib by unusual activation of pro-survival pathway
Disease Class: Lung adenocarcinoma [23]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Resistant Drug Seliciclib
 Drug Info 
Molecule Alteration Missense mutation
p.Y220C (c.659A>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell death detection ELISA assay
Mechanism Description The missense mutation p.Y220C (c.659A>G) in gene TP53 cause the resistance of Seliciclib by unusual activation of pro-survival pathway
Disease Class: Lung adenocarcinoma [23]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Resistant Drug Seliciclib
 Drug Info 
Molecule Alteration Missense mutation
p.Y234C (c.701A>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Cell death detection ELISA assay
Mechanism Description The missense mutation p.Y234C (c.701A>G) in gene TP53 cause the resistance of Seliciclib by unusual activation of pro-survival pathway
Tanespimycin
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Colorectal cancer [19]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Sensitive Drug Tanespimycin
 Drug Info 
Molecule Alteration Missense mutation
p.R248Q (c.743G>A)
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation JAKT2/STAT3 signaling pathway Inhibition hsa04030
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
H1299 cells Lung Homo sapiens (Human) CVCL_0060
SW1116 cells Colon Homo sapiens (Human) CVCL_0544
LS1034 cells Colon Homo sapiens (Human) CVCL_1382
SW48 cells Colon Homo sapiens (Human) CVCL_1724
Colo320 cells Colon Homo sapiens (Human) CVCL_1989
SW837 cells Colon Homo sapiens (Human) CVCL_1729
DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
SW1463 cells Rectum Homo sapiens (Human) CVCL_1718
In Vivo Model C57BL/6 mouse model Mus musculus
Experiment for
Molecule Alteration		 BCA protein assay; SDS-PAGE assay
Experiment for
Drug Resistance		 Scratch assay; Transwell migration assay; Fluorescent in situ hybridization assay
Mechanism Description The most common p53 mutant R248Q (mutp53) enhances Stat3 activation by binding to Stat3 and displacing SHP2 in colorectal cancer cells. Reduction of mutp53 genetically or by using the HSP90 inhibitor 17AAG reduces Stat3 signaling and the growth of mutp53-driven tumors.
Disease Class: Breast adenocarcinoma [18]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug Tanespimycin
 Drug Info 
Molecule Alteration Missense mutation
p.L194F (c.580C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
LY3009120
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Melanoma [20]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Sensitive Drug LY3009120
 Drug Info 
Molecule Alteration Missense mutation
p.D259Y (c.775G>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance		 CellTiter-Glo assay; Enzymatic kinase assay
Preclinical Drug(s)
10 drug(s) in total
Click to Show/Hide the Full List of Drugs
ALRN-6924
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Acute myeloid leukemia [24]
Resistant Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Resistant Drug ALRN-6924
 Drug Info 
Molecule Alteration Missense mutation
p.R248Q (c.743G>A)
Experimental Note Identified from the Human Clinical Data
AMGMDS3
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.V157F (c.469G>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.V157F (c.469G>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R158H (c.473G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R158H (c.473G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R158L (c.473G>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R158L (c.473G>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.Y220C (c.659A>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.Y220C (c.659A>G) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.G245S (c.733G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.G245S (c.733G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R248W (c.742C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R248W (c.742C>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R248Q (c.743G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R248Q (c.743G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R249S (c.747G>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R249S (c.747G>C) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R273C (c.817C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R273C (c.817C>T) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R273H (c.818G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R273H (c.818G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R280K (c.839G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R280K (c.839G>A) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [25]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AMGMDS3
 Drug Info 
Molecule Alteration Missense mutation
p.R280T (c.839G>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MG-63 cells Bone Homo sapiens (Human) CVCL_0426
NCI-H82 cells Pleural effusion Homo sapiens (Human) CVCL_1591
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Fluorescence microscopy assay
Mechanism Description The missense mutation p.R280T (c.839G>C) in gene TP53 cause the resistance of AMGMDS3 by unusual activation of pro-survival pathway
APR-246/Cisplatin
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: Peritoneal cancer [26]
Sensitive Disease Peritoneal cancer [ICD-11: 2C51.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.C135Y (c.404G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ascitic fluid .
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay
Disease Class: Fallopian tube cancer [26]
Sensitive Disease Fallopian tube cancer [ICD-11: 2C74.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.C238F (c.713G>T)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ascitic fluid .
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay
Disease Class: Ovarian cancer [26]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.L111Q (c.332T>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ascitic fluid .
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay
Disease Class: Ovarian cancer [26]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.P151H (c.452C>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ascitic fluid .
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay
Disease Class: Ovarian cancer [26]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.Y163H (c.487T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ascitic fluid .
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay
Disease Class: Ovarian cancer [26]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.P278R (c.833C>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ascitic fluid .
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay
Disease Class: Ovarian cancer [26]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.R280K (c.839G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ascitic fluid .
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Ovarian cancer [27]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.R248Q (c.743G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A2780-CP20 cells Ovary Homo sapiens (Human) CVCL_A5PS
In Vivo Model Female CD-1 Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay; WST-1 assay; Cell Titer-Glo assay; MTS assay
Disease Class: Lung adenocarcinoma [27]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.R248W (c.742C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A2780-CP20 cells Ovary Homo sapiens (Human) CVCL_A5PS
In Vivo Model Female CD-1 Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay; WST-1 assay; Cell Titer-Glo assay; MTS assay
Disease Class: Lung adenocarcinoma [27]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.R273H (c.818G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A2780-CP20 cells Ovary Homo sapiens (Human) CVCL_A5PS
In Vivo Model Female CD-1 Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay; WST-1 assay; Cell Titer-Glo assay; MTS assay
Disease Class: Lung adenocarcinoma [27]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug APR-246/Cisplatin
 Drug Info 
Molecule Alteration Missense mutation
p.Y163C (c.488A>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A2780-CP20 cells Ovary Homo sapiens (Human) CVCL_A5PS
In Vivo Model Female CD-1 Nu/Nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 FMCA assay; WST-1 assay; Cell Titer-Glo assay; MTS assay
CP-31398
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Cholangiocarcinoma [28]
Sensitive Disease Cholangiocarcinoma [ICD-11: 2C12.0]
 Disease Info 
Sensitive Drug CP-31398
 Drug Info 
Molecule Alteration Missense mutation
p.Y220C (c.659A>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Experiment for
Molecule Alteration		 qRT-PCR
Disease Class: Cholangiocarcinoma [28]
Sensitive Disease Cholangiocarcinoma [ICD-11: 2C12.0]
 Disease Info 
Sensitive Drug CP-31398
 Drug Info 
Molecule Alteration Missense mutation
p.R249S (c.747G>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
Experiment for
Molecule Alteration		 qRT-PCR
DS-7423
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Ovarian cancer [29]
Resistant Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Resistant Drug DS-7423
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model ES-2 cells Ovary Homo sapiens (Human) CVCL_3509
TOV-21 cells Ovary Homo sapiens (Human) CVCL_3613
SKOV5 cells Ovary Homo sapiens (Human) N.A.
RMG-I cells Ascites Homo sapiens (Human) CVCL_1662
OVTOKO cells Spleen Homo sapiens (Human) CVCL_3117
OVSAHO cells Abdomen Homo sapiens (Human) CVCL_3114
OVMANA cells Ovary Homo sapiens (Human) CVCL_3111
OVKATE cells Ovary Homo sapiens (Human) CVCL_3110
OVISE cells Pelvi Homo sapiens (Human) CVCL_3116
OV1063 cells Ascites Homo sapiens (Human) CVCL_4366
SKOV5 cells Ovary Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis; Luciferase assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Ovarian cancer [29]
Resistant Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Resistant Drug DS-7423
 Drug Info 
Molecule Alteration Missense mutation
p.S241F (c.722C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model ES-2 cells Ovary Homo sapiens (Human) CVCL_3509
TOV-21 cells Ovary Homo sapiens (Human) CVCL_3613
SKOV6 cells Uterus Homo sapiens (Human) CVCL_A457
RMG-I cells Ascites Homo sapiens (Human) CVCL_1662
OVTOKO cells Spleen Homo sapiens (Human) CVCL_3117
OVSAHO cells Abdomen Homo sapiens (Human) CVCL_3114
OVMANA cells Ovary Homo sapiens (Human) CVCL_3111
OVKATE cells Ovary Homo sapiens (Human) CVCL_3110
OVISE cells Pelvi Homo sapiens (Human) CVCL_3116
OV1063 cells Ascites Homo sapiens (Human) CVCL_4366
SKOV6 cells Uterus Homo sapiens (Human) CVCL_A457
Experiment for
Molecule Alteration		 Western blotting analysis; Luciferase assay
Experiment for
Drug Resistance		 CCK-8 assay
HSP90 inhibitor
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Solid tumour/cancer [18]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug HSP90 inhibitor
 Drug Info 
Molecule Alteration Missense mutation
p.R248Q (c.743G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
Disease Class: Solid tumour/cancer [18]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug HSP90 inhibitor
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
H1975 cells Lung Homo sapiens (Human) CVCL_1511
T47D cells Breast Homo sapiens (Human) CVCL_0553
ES2 cells Ovary Homo sapiens (Human) CVCL_AX39
DU145 cells Prostate Homo sapiens (Human) CVCL_0105
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-46 cells N.A. Homo sapiens (Human) N.A.
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
EFO21 cells Ascites Homo sapiens (Human) CVCL_0029
COV434 cells N.A. Homo sapiens (Human) CVCL_2010
COLO704 cells Ascites Homo sapiens (Human) CVCL_1994
HOC7 cells Ascites Homo sapiens (Human) CVCL_5455
In Vivo Model Athymic (nu/nu) male xenograft mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; Quantitative PCR analysis
Experiment for
Drug Resistance		 CellTiter-blue cell viability assay
NSC319726
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Breast adenocarcinoma [30]
Resistant Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Resistant Drug NSC319726
 Drug Info 
Molecule Alteration Missense mutation
p.R273W (c.817_819delCGTinsTGG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model (MEF) (10)3 cells N.A. Mus musculus (Mouse) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.R273W (c.817_819delCGTinsTGG) in gene TP53 cause the resistance of NSC319726 by aberration of the drug's therapeutic target
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Breast adenocarcinoma [30]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug NSC319726
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model (MEF) (10)3 cells N.A. Mus musculus (Mouse) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the sensitivity of NSC319726 by aberration of the drug's therapeutic target
Disease Class: Lung adenocarcinoma [30]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug NSC319726
 Drug Info 
Molecule Alteration Missense mutation
p.R175L (c.524G>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model (MEF) (10)3 cells N.A. Mus musculus (Mouse) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.R175L (c.524G>T) in gene TP53 cause the sensitivity of NSC319726 by aberration of the drug's therapeutic target
Disease Class: Ovarian cancer [30]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug NSC319726
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model (MEF) (10)3 cells N.A. Mus musculus (Mouse) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the sensitivity of NSC319726 by aberration of the drug's therapeutic target
NSC59984
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Colorectal cancer [31]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Sensitive Drug NSC59984
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
RXF393 cells Kidney Homo sapiens (Human) CVCL_1673
MRC5 cells Fetal lung Homo sapiens (Human) CVCL_0440
Wi38 cells Fetal lung Homo sapiens (Human) CVCL_0579
Hop92 cells Lung Homo sapiens (Human) CVCL_1286
In Vivo Model Female CRL nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Semi-quantitative RT-PCR; Western blotting analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; Colony formation assay
Disease Class: Colorectal cancer [31]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Sensitive Drug NSC59984
 Drug Info 
Molecule Alteration Missense mutation
p.R175L (c.524G>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
DLD-1 cells Colon Homo sapiens (Human) CVCL_0248
RXF393 cells Kidney Homo sapiens (Human) CVCL_1673
MRC5 cells Fetal lung Homo sapiens (Human) CVCL_0440
Wi38 cells Fetal lung Homo sapiens (Human) CVCL_0579
Hop92 cells Lung Homo sapiens (Human) CVCL_1286
In Vivo Model Female CRL nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Semi-quantitative RT-PCR; Western blotting analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; Colony formation assay
ReACp53
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Ovarian cancer [32]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug ReACp53
 Drug Info 
Molecule Alteration Missense mutation
p.Y327L (c.979_980delTAinsCT)
Experimental Note Identified from the Human Clinical Data
In Vitro Model S1 GODL cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Immunocompromised NSG mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 In vitro 3D organoid assay
Disease Class: Solid tumour/cancer [32]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ReACp53
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model S1 GODL cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Immunocompromised NSG mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 In vitro 3D organoid assay
Disease Class: Head and neck cancer [32]
Sensitive Disease Head and neck cancer [ICD-11: 2D42.0]
 Disease Info 
Sensitive Drug ReACp53
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model S1 GODL cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Immunocompromised NSG mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 In vitro 3D organoid assay
Disease Class: Ovarian cancer [32]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug ReACp53
 Drug Info 
Molecule Alteration Missense mutation
p.R248Q (c.743G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model S1 GODL cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Immunocompromised NSG mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 In vitro 3D organoid assay
Disease Class: Ovarian cancer [32]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Sensitive Drug ReACp53
 Drug Info 
Molecule Alteration Missense mutation
p.Y234C (c.701A>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model S1 GODL cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Immunocompromised NSG mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 In vitro 3D organoid assay
YW3-56
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: ER negative breast cancer [33]
Sensitive Disease ER negative breast cancer [ICD-11: 2C60.7]
 Disease Info 
Sensitive Drug YW3-56
 Drug Info 
Molecule Alteration Missense mutation
p.R280K (c.839G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
1833TR cells N.A. . N.A.
In Vivo Model Female xenograft nude mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Investigative Drug(s)
3 drug(s) in total
Click to Show/Hide the Full List of Drugs
EAP Protocol
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Gastric adenocarcinoma [34]
Sensitive Disease Gastric adenocarcinoma [ICD-11: 2B72.0]
 Disease Info 
Sensitive Drug EAP Protocol
 Drug Info 
Molecule Alteration Missense mutation
p.R282L (c.845G>T)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Stomach .
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.R282L (c.845G>T) in gene TP53 cause the sensitivity of EAP Protocol by unusual activation of pro-survival pathway
Disease Class: Gastric adenocarcinoma [34]
Sensitive Disease Gastric adenocarcinoma [ICD-11: 2B72.0]
 Disease Info 
Sensitive Drug EAP Protocol
 Drug Info 
Molecule Alteration Missense mutation
p.R175H (c.524G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Stomach .
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.R175H (c.524G>A) in gene TP53 cause the sensitivity of EAP Protocol by unusual activation of pro-survival pathway
Disease Class: Gastric adenocarcinoma [34]
Sensitive Disease Gastric adenocarcinoma [ICD-11: 2B72.0]
 Disease Info 
Sensitive Drug EAP Protocol
 Drug Info 
Molecule Alteration Missense mutation
p.R213P (c.638G>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Stomach .
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.R213P (c.638G>C) in gene TP53 cause the sensitivity of EAP Protocol by unusual activation of pro-survival pathway
PKI-587
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Lung adenocarcinoma [35]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug PKI-587
 Drug Info 
Molecule Alteration Missense mutation
p.R158G (c.472C>G)
Experimental Note Identified from the Human Clinical Data
Purine analogues
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Chronic lymphocytic leukemia [36]
Resistant Disease Chronic lymphocytic leukemia [ICD-11: 2A82.0]
 Disease Info 
Resistant Drug Purine analogues
 Drug Info 
Molecule Alteration Mutation
.
Experimental Note Identified from the Human Clinical Data
In Vitro Model Bone marrow Blood Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Sanger sequencing assay; Next-generation sequencing assay
Experiment for
Drug Resistance		 karyotyping assay
Mechanism Description TP53 abnormalities lead to resistance to purine a.logues and are found in over 40% of patients with refractory chronic lymphocytic leukemia (CLL).
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
Click to Show/Hide the Resistance Disease of This Class
Brain cancer [ICD-11: 2A00]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Nervous tissue
The Specified Disease Brain cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 3.42E-178; Fold-change: 1.18E+00; Z-score: 2.70E+00
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
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The Studied Tissue Brainstem tissue
The Specified Disease Glioma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 2.93E-02; Fold-change: 2.69E-01; Z-score: 2.34E+00
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
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The Studied Tissue White matter
The Specified Disease Glioma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 2.95E-02; Fold-change: 3.97E-01; Z-score: 7.90E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
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The Studied Tissue Brainstem tissue
The Specified Disease Neuroectodermal tumor
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 8.74E-01; Fold-change: -1.33E-01; Z-score: -6.77E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
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Chronic myeloid leukemia [ICD-11: 2A20]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Whole blood
The Specified Disease Myelofibrosis
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 1.02E-05; Fold-change: -6.91E-01; Z-score: -3.13E+00
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the disease section of the tissue
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The Studied Tissue Whole blood
The Specified Disease Polycythemia vera
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 4.56E-24; Fold-change: -7.55E-01; Z-score: -3.26E+00
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Acute myeloid leukemia [ICD-11: 2A60]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Bone marrow
The Specified Disease Acute myeloid leukemia
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 7.90E-07; Fold-change: 2.95E-01; Z-score: 5.95E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Gastric cancer [ICD-11: 2B72]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Gastric tissue
The Specified Disease Gastric cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 1.43E-01; Fold-change: 2.14E-01; Z-score: 5.31E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 1.31E-04; Fold-change: 1.18E+00; Z-score: 1.51E+00
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section
Download Molecule expression data of patients in the disease section of the tissue
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Liver cancer [ICD-11: 2C12]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Liver
The Specified Disease Liver cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 2.64E-02; Fold-change: 1.46E-01; Z-score: 2.81E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 3.27E-17; Fold-change: 7.65E-01; Z-score: 1.14E+00
The Expression Level of Disease Section Compare with the Other Disease Section p-value: 7.04E-01; Fold-change: 2.46E-01; Z-score: 3.20E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Molecule expression in tissue other than the diseased tissue of patients
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Download Molecule expression data in the tissue of the other disease section
Lung cancer [ICD-11: 2C25]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Lung
The Specified Disease Lung cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 9.24E-02; Fold-change: -1.28E-02; Z-score: -2.15E-02
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 1.01E-01; Fold-change: -3.27E-01; Z-score: -4.78E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Melanoma [ICD-11: 2C30]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Skin
The Specified Disease Melanoma
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 3.47E-01; Fold-change: 1.46E-01; Z-score: 2.20E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Breast cancer [ICD-11: 2C60]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Breast tissue
The Specified Disease Breast cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 5.63E-01; Fold-change: 1.62E-02; Z-score: 1.76E-02
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 7.38E-02; Fold-change: -1.63E-01; Z-score: -1.55E-01
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Ovarian cancer [ICD-11: 2C73]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Ovary
The Specified Disease Ovarian cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 4.96E-01; Fold-change: 7.27E-02; Z-score: 1.17E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 3.50E-04; Fold-change: 1.14E+00; Z-score: 1.72E+00
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the normal section of the tissue adjacent to the disease section
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Bladder cancer [ICD-11: 2C94]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Bladder tissue
The Specified Disease Bladder cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 5.97E-02; Fold-change: -1.24E-01; Z-score: -4.64E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the disease section of the tissue
Download Molecule expression data in the tissue of healthy individual
Head and neck cancer [ICD-11: 2D42]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Head and neck tissue
The Specified Disease Head and neck cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 1.22E-01; Fold-change: 2.20E-01; Z-score: 4.71E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
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Download Molecule expression data in the tissue of healthy individual
ICD Disease Classification 15
Click to Show/Hide the Resistance Disease of This Class
Rheumatoid arthritis [ICD-11: FA20]
Click to Show/Hide
Differential expression of molecule in resistant diseases
The Studied Tissue Peripheral blood
The Specified Disease Rheumatoid arthritis
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 1.42E-04; Fold-change: -5.49E-02; Z-score: -1.83E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
Download Molecule expression data of patients in the disease section of the tissue
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The Studied Tissue Synovial tissue
The Specified Disease Rheumatoid arthritis
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 9.88E-11; Fold-change: 2.48E+00; Z-score: 1.06E+01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Download Molecule expression barchart for all samples
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Tissue-specific Molecule Abundances in Healthy Individuals
Click to Show/Hide the Molecule Abundances
Download the Tissue-Specific Variation(s) Profile
References
Ref 1 Longitudinal copy number, whole exome and targeted deep sequencing of 'good risk' IGHV-mutated CLL patients with progressive disease. Leukemia. 2016 Jun;30(6):1301-10. doi: 10.1038/leu.2016.10. Epub 2016 Feb 5.
Ref 2 Carboplatin-docetaxel-induced activity against ovarian cancer is dependent on up-regulated lncRNA PVT1. Int J Clin Exp Pathol. 2015 Apr 1;8(4):3803-10. eCollection 2015.
Ref 3 The long noncoding RNA HIF1A-AS2 facilitates cisplatin resistance in bladder cancer. J Cell Biochem. 2019 Jan;120(1):243-252. doi: 10.1002/jcb.27327. Epub 2018 Sep 14.
Ref 4 Has miR 125a and 125b are induced by treatment with cisplatin in nasopharyngeal carcinoma and inhibit apoptosis in a p53 dependent manner by targeting p53 mRNA. Mol Med Rep. 2015 Sep;12(3):3569-3574. doi: 10.3892/mmr.2015.3863. Epub 2015 May 27.
Ref 5 Downregulated long non-coding RNA TRPM2-AS inhibits cisplatin resistance of non-small cell lung cancer cells via activation of p53- p66shc pathway. Eur Rev Med Pharmacol Sci. 2017 Jun;21(11):2626-2634.
Ref 6 Downregulation of Meg3 enhances cisplatin resistance of lung cancer cells through activation of the WNT/Beta-catenin signaling pathway. Mol Med Rep. 2015 Sep;12(3):4530-4537. doi: 10.3892/mmr.2015.3897. Epub 2015 Jun 8.
Ref 7 Bone interface modulates drug resistance in breast cancer bone metastasis .Colloids Surf B Biointerfaces. 2020 Nov;195:111224. doi: 10.1016/j.colsurfb.2020.111224. Epub 2020 Jun 26. 10.1016/j.colsurfb.2020.111224
Ref 8 miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor. Cancer Cell Int. 2013 Mar 4;13(1):21. doi: 10.1186/1475-2867-13-21.
Ref 9 Long non-coding RNA 00607 as a tumor suppressor by modulating NF-kB p65/p53 signaling axis in hepatocellular carcinoma. Carcinogenesis. 2018 Dec 31;39(12):1438-1446. doi: 10.1093/carcin/bgy113.
Ref 10 Knockdown of microRNA-127 reverses adriamycin resistance via cell cycle arrest and apoptosis sensitization in adriamycin-resistant human glioma cells. Int J Clin Exp Pathol. 2015 Jun 1;8(6):6107-16. eCollection 2015.
Ref 11 FLT3 Inhibitors in Acute Myeloid Leukemia: Current Status and Future Directions. Mol Cancer Ther. 2017 Jun;16(6):991-1001. doi: 10.1158/1535-7163.MCT-16-0876.
Ref 12 Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013 May 2;497(7447):108-12. doi: 10.1038/nature12065. Epub 2013 Apr 7.
Ref 13 Drug-resistance in rheumatoid arthritis: the role of p53 gene mutations, ABC family transporters and personal factors .Curr Opin Pharmacol. 2020 Oct;54:59-71. doi: 10.1016/j.coph.2020.08.002. Epub 2020 Sep 14. 10.1016/j.coph.2020.08.002
Ref 14 Over expression of miR-200c suppresses invasion and restores methotrexate sensitivity in lung cancer A549 cells. Gene. 2016 Nov 30;593(2):265-71. doi: 10.1016/j.gene.2016.07.038. Epub 2016 Jul 16.
Ref 15 Paclitaxel promotes lung cancer cell apoptosis via MEG3-P53 pathway activation. Biochem Biophys Res Commun. 2018 Sep 26;504(1):123-128. doi: 10.1016/j.bbrc.2018.08.142. Epub 2018 Aug 31.
Ref 16 Dissecting Genomic Aberrations in Myeloproliferative Neoplasms by Multiplex-PCR and Next Generation Sequencing. PLoS One. 2015 Apr 20;10(4):e0123476. doi: 10.1371/journal.pone.0123476. eCollection 2015.
Ref 17 Anti-Apoptotic Effects of Resistance Training and Tribulus Terrestris Consumption in the Heart Tissue of Rats Exposed to Stanozolol .Eurasian J Med. 2021 Jun;53(2):79-84. doi: 10.5152/eurasianjmed.2021.20051. 10.5152/eurasianjmed.2021.20051
Ref 18 Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatmentNature. 2015 Jul 16;523(7560):352-6. doi: 10.1038/nature14430. Epub 2015 May 25.
Ref 19 Therapeutic Ablation of Gain-of-Function Mutant p53 in Colorectal Cancer Inhibits Stat3-Mediated Tumor Growth and InvasionCancer Cell. 2018 Aug 13;34(2):298-314.e7. doi: 10.1016/j.ccell.2018.07.004.
Ref 20 Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant CancersCancer Cell. 2015 Sep 14;28(3):384-98. doi: 10.1016/j.ccell.2015.08.002. Epub 2015 Sep 3.
Ref 21 PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53Clin Cancer Res. 2011 May 1;17(9):2830-41. doi: 10.1158/1078-0432.CCR-10-3168. Epub 2011 Mar 17.
Ref 22 Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancerJ Clin Oncol. 2012 Oct 10;30(29):3633-9. doi: 10.1200/JCO.2011.40.7783. Epub 2012 Sep 10.
Ref 23 Roscovitine-induced apoptosis of H1299 cells depends on functional status of p53Neoplasma. 2012;59(6):606-12. doi: 10.4149/neo_2012_077.
Ref 24 Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemiaSci Transl Med. 2018 Apr 11;10(436):eaao3003. doi: 10.1126/scitranslmed.aao3003.
Ref 25 Identifying the determinants of response to MDM2 inhibitionOncotarget. 2015 Apr 10;6(10):7701-12. doi: 10.18632/oncotarget.3116.
Ref 26 Strong synergy with APR-246 and DNA-damaging drugs in primary cancer cells from patients with TP53 mutant High-Grade Serous ovarian cancerJ Ovarian Res. 2016 May 14;9(1):27. doi: 10.1186/s13048-016-0239-6.
Ref 27 APR-246 overcomes resistance to cisplatin and doxorubicin in ovarian cancer cellsCell Death Dis. 2015 Jun 18;6(6):e1794. doi: 10.1038/cddis.2015.143.
Ref 28 CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivoTumour Biol. 2016 Jan;37(1):807-15. doi: 10.1007/s13277-015-3857-5. Epub 2015 Aug 7.
Ref 29 Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423PLoS One. 2014 Feb 4;9(2):e87220. doi: 10.1371/journal.pone.0087220. eCollection 2014.
Ref 30 Allele-specific p53 mutant reactivationCancer Cell. 2012 May 15;21(5):614-625. doi: 10.1016/j.ccr.2012.03.042.
Ref 31 Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53Cancer Res. 2015 Sep 15;75(18):3842-52. doi: 10.1158/0008-5472.CAN-13-1079. Epub 2015 Aug 20.
Ref 32 A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian CarcinomasCancer Cell. 2016 Jan 11;29(1):90-103. doi: 10.1016/j.ccell.2015.12.002. Epub 2015 Dec 31.
Ref 33 ATF4 Gene Network Mediates Cellular Response to the Anticancer PAD Inhibitor YW3-56 in Triple-Negative Breast Cancer CellsMol Cancer Ther. 2015 Apr;14(4):877-88. doi: 10.1158/1535-7163.MCT-14-1093-T. Epub 2015 Jan 22.
Ref 34 Alterations in p53 predict response to preoperative high dose chemotherapy in patients with gastric cancerMol Pathol. 2003 Oct;56(5):286-92. doi: 10.1136/mp.56.5.286.
Ref 35 Integrative radiogenomic profiling of squamous cell lung cancerCancer Res. 2013 Oct 15;73(20):6289-98. doi: 10.1158/0008-5472.CAN-13-1616. Epub 2013 Aug 26.
Ref 36 TP53 mutations are early events in chronic lymphocytic leukemia disease progression and precede evolution to complex karyotypes. Int J Cancer. 2016 Oct 15;139(8):1759-63. doi: 10.1002/ijc.30222. Epub 2016 Jun 24.

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