Molecule Information

General Information of the Molecule (ID: Mol00065)
Name
Receptor tyrosine-protein kinase erbB-2 (ERBB2) ,Homo sapiens
Molecule Type
Protein
Gene Name
ERBB2
Gene ID
2064
Location
chr17:39687914-39730426[+]
Sequence
MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNL
ELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNG
DPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLA
LTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQC
AAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACP
YNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSAN
IQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLP
DLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTV
PWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQEC
VEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARC
PSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVG
ILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETEL
RKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSP
YVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR
LVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFT
HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWM
IDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDA
EEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEG
AGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYV
NQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQ
GGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV
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Function
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.
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Uniprot ID
ERBB2_HUMAN
Ensembl ID
ENSG00000141736
HGNC ID
HGNC:3430
        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
  RTDM: Regulation by the Disease Microenvironment
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
16 drug(s) in total
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Cetuximab
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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: Colorectal cancer [1]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Structural variation
Amplification
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations.
Disease Class: Colorectal cancer [2]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Resistant Drug Cetuximab
 Drug Info 
Molecule Alteration Structural variation
Amplification
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Sanger sequencing assay; Next-generation sequencing assay
Mechanism Description Mutations in kRAS, NRAS, and BRAF and amplification of ERBB2 and MET drive primary (de novo) resistance to anti-EGFR treatment.
Cisplatin
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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: Gastric cancer [3]
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
mTOR signaling pathway Inhibition hsa04150
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.
Disease Class: Gastric cancer [4]
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Inhibition hsa05200
In Vitro Model BGC-823 cells Gastric Homo sapiens (Human) CVCL_3360
MGC-803 cells Gastric Homo sapiens (Human) CVCL_5334
SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
AGS cells Gastric Homo sapiens (Human) CVCL_0139
HGC27 cells Gastric Homo sapiens (Human) CVCL_1279
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Overexpression of miR-125b improved the chemosensitivity of DDP in HGC-27 and MGC-803 cells and miR-125b obviously inhibited the expression of HER2 at protein level in HGC-27 and MGC-803 cells.
Dacomitinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Dacomitinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [6]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration Complex-indel
p.M774_774delinsWLV (c.2320_2322delinsTGGCTTGTA)
Experimental Note Identified from the Human Clinical Data
In Vitro Model NSCLC cells Lung Homo sapiens (Human) N.A.
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model BALB/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; SDS-PAGE assay
Experiment for
Drug Resistance		 MTS assay; Crystal violet staining assay
Mechanism Description Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.
Disease Class: Solid tumour/cancer [6]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)
Experimental Note Identified from the Human Clinical Data
In Vitro Model NSCLC cells Lung Homo sapiens (Human) N.A.
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model BALB/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; SDS-PAGE assay
Experiment for
Drug Resistance		 MTS assay; Crystal violet staining assay
Mechanism Description Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.
Disease Class: Solid tumour/cancer [6]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration IF-insertion
p.G778_S779insCPG (c.2335_2336insGTCCTGGTT)
Experimental Note Identified from the Human Clinical Data
In Vitro Model NSCLC cells Lung Homo sapiens (Human) N.A.
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model BALB/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis; SDS-PAGE assay
Experiment for
Drug Resistance		 MTS assay; Crystal violet staining assay
Mechanism Description Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.
Disease Class: Lung adenocarcinoma [7]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration Complex-indel
p.M774_774delinsWLV (c.2320_2322delinsTGGCTTGTA)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Lung .
Experiment for
Molecule Alteration		 DNA sequencing assay
Experiment for
Drug Resistance		 Clinical measurement assay
Disease Class: Lung adenocarcinoma [7]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Lung .
Experiment for
Molecule Alteration		 DNA sequencing assay
Experiment for
Drug Resistance		 Clinical measurement assay
Disease Class: Lung adenocarcinoma [7]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration IF-insertion
p.P780_Y781 (c.2340_2341)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Lung .
Experiment for
Molecule Alteration		 DNA sequencing assay
Experiment for
Drug Resistance		 Clinical measurement assay
Disease Class: Lung adenocarcinoma [7]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration Complex-indel
p.M774delinsWLV (c.2320delinsTGGCTGG)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Lung .
Experiment for
Molecule Alteration		 DNA sequencing assay
Experiment for
Drug Resistance		 Clinical measurement assay
Disease Class: Lung adenocarcinoma [7]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration Duplication
p.P780_Y781 (c.2340_2341)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Lung .
Experiment for
Molecule Alteration		 DNA sequencing assay
Experiment for
Drug Resistance		 Clinical measurement assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Dacomitinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Doxorubicin
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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: Breast cancer [8]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
Experiment for
Molecule Alteration		 Western blot analysis; Dual luciferase reporter assay
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometric analysis; Transwell invasion assay
Mechanism Description miR1268b confers chemosensitivity in breast cancer by targeting ERBB2-mediated PI3k-AkT pathway. miR1268b could repress the PI3k-AkT signaling pathway by targeting ERBB2 and inhibit the anti-apoptosis protein Bcl2.
Disease Class: Gastric cancer [3]
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
mTOR signaling pathway Inhibition hsa04150
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.
Disease Class: Chondrosarcoma [9]
Sensitive Disease Chondrosarcoma [ICD-11: 2B50.0]
 Disease Info 
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
Glucose metabolism signaling pathway Regulation hsa05230
In Vitro Model CH-2879 cells Bone Homo sapiens (Human) CVCL_9921
OUMS-27 cells Bone Homo sapiens (Human) CVCL_3090
SW1353 cells Bone Homo sapiens (Human) CVCL_0543
CS-1 cells Bone Homo sapiens (Human) CVCL_T023
CSPG cells Bone Homo sapiens (Human) N.A.
JJ012 cells Bone Homo sapiens (Human) CVCL_D605
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-125b was downregulated in chondrosarcoma cells compared with normal human chondrocytes. More importantly, miR-125b was downregulated in doxorubicin resistant cancer cells, with its overexpression enhancing doxorubicin-induced cytotoxicity and apoptosis, subsequently increasing the sensitivity of chondrosarcoma cells to doxorubicin. ErbB2 was a direct target of miR-125b in chondrosarcoma cells. The inhibition of ErbB2 by overexpression of miR-125b led to suppression of glucose metabolism, which rendered chondrosarcoma cells susceptible to doxorubicin. Restoring the expression of ErbB2 and glucose metabolic enzymes recovered doxorubicin resistance in counteracting miR-125b-mediated sensitivity. Taken together, miR-125b plays a critical role in doxorubicin resistance through suppression of ErbB2-induced glucose metabolism, and it may serve as a potential target for overcoming chemoresistance in human chondrosarcoma.
Erlotinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Erlotinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Erlotinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Erlotinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: EGFR-mutant non-small cell lung cancer [10]
Resistant Disease EGFR-mutant non-small cell lung cancer [ICD-11: 2C25.7]
 Disease Info 
Resistant Drug Erlotinib
 Drug Info 
Molecule Alteration Structural variation
Copy number gain
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Low throughput experiment assay
Experiment for
Drug Resistance		 Progression-free survival assay
Mechanism Description Acquired resistance can occur through failure of drug delivery to the target, as in isolated central nervous system (CNS) progression, or by selection of biological variants during TkI exposure.
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: Gastric cancer [3]
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Sensitive Drug Fluorouracil
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
mTOR signaling pathway Inhibition hsa04150
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.
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: EGFR-mutant non-small cell lung cancer [10]
Resistant Disease EGFR-mutant non-small cell lung cancer [ICD-11: 2C25.7]
 Disease Info 
Resistant Drug Gefitinib
 Drug Info 
Molecule Alteration Structural variation
Copy number gain
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Low throughput experiment assay
Experiment for
Drug Resistance		 Progression-free survival assay
Mechanism Description Acquired resistance can occur through failure of drug delivery to the target, as in isolated central nervous system (CNS) progression, or by selection of biological variants during TkI exposure.
Lapatinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: HER2 positive breast cancer [11]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Resistant Drug Lapatinib
 Drug Info 
Molecule Alteration Missense mutation
p.L755S (c.2263_2264delCTinsAG)
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation HER2 signaling pathway Activation hsa04012
In Vitro Model AU565 cells Breast Homo sapiens (Human) CVCL_1074
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
BT474/AZ cells Breast Homo sapiens (Human) CVCL_0179
In Vivo Model Athymic mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description HER2 reactivation through acquisition of the HER2L755S mutation was identified as a mechanism of acquired resistance to L-containing HER2-targeted therapy in preclinical HER2-amplified breast cancer models, which can be overcome by irreversible HER1/2 inhibitors.
Disease Class: HER2 positive breast cancer [12]
Resistant Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Resistant Drug Lapatinib
 Drug Info 
Molecule Alteration Missense mutation
p.T798M (c.2393_2394delCAinsTG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model BT474 cells Breast Homo sapiens (Human) CVCL_0179
MCF10A cells Breast Homo sapiens (Human) CVCL_0598
In Vivo Model Athymic female mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 HER2T798M sequencing assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the resistance of Lapatinib by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Lapatinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Lapatinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Lapatinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast cancer [13]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Resistant Drug Lapatinib
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
ERRB2/3 signaling pathway Activation hsa04210
In Vitro Model ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 WST-1 proliferation assay
Mechanism Description Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) Drives Proliferation of IPH-926 lobular Carcinoma Cells. Relative high BCAR4 mRNA expression was identified in IPH-926, a cell line derived from an endocrine-resistant lobular breast cancer. Moderate BCAR4 expression was evident in MDA-MB-134 and MDA-MB-453 breast cancer cells. BCAR4 protein was detected in breast cancer cells with ectopic (ZR-75-1-BCAR4) and endogenous (IPH-926, MDA-MB-453) BCAR4 mRNA expression. knockdown of BCAR4 inhibited cell proliferation. A similar effect was observed upon knockdown of ERBB2/3 and exposure to lapatinib, implying that BCAR4 acts in an ERBB2/3-dependent manner.BCAR4 encodes a functional protein, which drives proliferation of endocrine-resistant breast cancer cells. Lapatinib, a clinically approved EGFR/ERBB2 inhibitor, counteracts BCAR4-driven tumor cell growth, a clinical relevant observation.
Mitomycin
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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: Gastric cancer [3]
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Sensitive Drug Mitomycin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
mTOR signaling pathway Inhibition hsa04150
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.
Neratinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Neratinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: HER2 negative breast cancer [14]
Sensitive Disease HER2 negative breast cancer [ICD-11: 2C60.11]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Missense mutation
p.L755S (c.2263_2264delCTinsAG)
Experimental Note Identified from the Human Clinical Data
Disease Class: HER2 negative breast cancer [14]
Sensitive Disease HER2 negative breast cancer [ICD-11: 2C60.11]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Complex-indel
p.L755_E757delinsS (c.2263_2271delinsAGC)
Experimental Note Identified from the Human Clinical Data
Disease Class: HER2 negative breast cancer [14]
Sensitive Disease HER2 negative breast cancer [ICD-11: 2C60.11]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Identified from the Human Clinical Data
Disease Class: HER2 negative breast cancer [14]
Sensitive Disease HER2 negative breast cancer [ICD-11: 2C60.11]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Missense mutation
p.V777L (c.2329G>C)
Experimental Note Identified from the Human Clinical Data
Disease Class: HER2 negative breast cancer [14]
Sensitive Disease HER2 negative breast cancer [ICD-11: 2C60.11]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)
Experimental Note Identified from the Human Clinical Data
Disease Class: HER2 negative breast cancer [14]
Sensitive Disease HER2 negative breast cancer [ICD-11: 2C60.11]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Missense mutation
p.L869R (c.2606T>G)
Experimental Note Identified from the Human Clinical Data
Disease Class: HER2 negative breast cancer [14]
Sensitive Disease HER2 negative breast cancer [ICD-11: 2C60.11]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Missense mutation
p.S310F (c.929C>T)
Experimental Note Identified from the Human Clinical Data
Osimertinib
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: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Osimertinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Osimertinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Osimertinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Panitumumab
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: Colorectal cancer [1]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Resistant Drug Panitumumab
 Drug Info 
Molecule Alteration Structural variation
Amplification
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Liquid biopsy assay
Mechanism Description Mechanisms of resistance to EGFR blockade include the emergence of kRAS, NRAS and EGFR extracellular domain mutations as well as HER2/MET alterations.
Tamoxifen
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 cancer [15]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Sensitive Drug Tamoxifen
 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
T47D cells Breast Homo sapiens (Human) CVCL_0553
MCF7/TAMR cells Breast Homo sapiens (Human) CVCL_EG55
T47D/TAMR cells Breast Homo sapiens (Human) CVCL_1D36
Experiment for
Molecule Alteration		 Western blot analysis; Luciferase reporter assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The ERBB2 expression is regulated at the post-transcriptional level by miR26a/b and the RNA-binding protein human antigen R, miR26a/b inhibits the translation of ERBB2 mRNA, whereas HuR enhances the stability of the ERBB2 mRNA.
Trastuzumab
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Disease Class: Breast cancer [16]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Resistant Drug Trastuzumab
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell viability Inhibition hsa05200
miR125b/HER2/Snail1 signaling pathway Regulation hsa05206
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
BT474 cells Breast Homo sapiens (Human) CVCL_0179
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Wound-healing assay; Transwell assay
Mechanism Description TINCR, which is transcriptionally activated by H3k27 acetylation, upregulates HER-2 expression by downregulating miR-125b and TINCR promotes trastuzumab resistance-induced EMT by directly targeting Snail-1.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: HER2 positive breast cancer [17]
Sensitive Disease HER2 positive breast cancer [ICD-11: 2C60.8]
 Disease Info 
Sensitive Drug Trastuzumab
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
HER2 signaling pathway Activation hsa04012
In Vitro Model SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
BT474 cells Breast Homo sapiens (Human) CVCL_0179
Experiment for
Molecule Alteration		 Western blot analysis; RT-qPCR
Experiment for
Drug Resistance		 WST1 assay
Mechanism Description miR-770-5p overexpression downregulated HER2 and increased the effect of trastuzumab.
Trastuzumab-based chemotherapy
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: Head and neck cancer [18]
Sensitive Disease Head and neck cancer [ICD-11: 2D42.0]
 Disease Info 
Sensitive Drug Trastuzumab-based chemotherapy
 Drug Info 
Molecule Alteration Copy number gain
.
Experimental Note Identified from the Human Clinical Data
In Vitro Model Human salivary ductal carcinoma tissue .
Mechanism Description The copy number gain in gene ERBB2 cause the sensitivity of Trastuzumab-based chemotherapy by aberration of the drug's therapeutic target.
Disease Class: Lung adenocarcinoma [19]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Trastuzumab-based chemotherapy
 Drug Info 
Molecule Alteration Missense mutation
p.G776L (c.2326_2327delGGinsCT)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Lung .
Mechanism Description The missense mutation p.G776L (c.2326_2327delGGinsCT) in gene ERBB2 cause the sensitivity of Trastuzumab-based chemotherapy by aberration of the drug's therapeutic target
Tucatinib
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: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Tucatinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Tucatinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Tucatinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Clinical Trial Drug(s)
9 drug(s) in total
Click to Show/Hide the Full List of Drugs
Buparlisib
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 [12]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug Buparlisib
 Drug Info 
Molecule Alteration Missense mutation
p.T798M (c.2393_2394delCAinsTG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model BT474 cells Breast Homo sapiens (Human) CVCL_0179
MCF10A cells Breast Homo sapiens (Human) CVCL_0598
In Vivo Model Athymic female mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 HER2T798M sequencing assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the sensitivity of Buparlisib by aberration of the drug's therapeutic target
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: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA + p.C805S
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Ganetespib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA + p.C805S
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Selumetinib
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: Bladder cancer [20]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Resistant Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.S310F (c.929C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
T24 cells Bladder Homo sapiens (Human) CVCL_0554
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
HT1376 cells Bladder Homo sapiens (Human) CVCL_1292
RT112 cells Bladder Homo sapiens (Human) CVCL_1670
TCCSuP cells Bladder Homo sapiens (Human) CVCL_1738
UM-UC3 cells Urinary bladder Homo sapiens (Human) CVCL_1783
WH cells Bladder Homo sapiens (Human) CVCL_0C39
VM-CUBIII cells Urinary bladder Homo sapiens (Human) CVCL_9830
VM-CUBII cells Urinary bladder Homo sapiens (Human) CVCL_9829
VM-CUBI cells Obturator lymph node Homo sapiens (Human) CVCL_1786
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
TSU-PR1 cells Urinary bladder Homo sapiens (Human) CVCL_4014
SW1710 cells Bladder Homo sapiens (Human) CVCL_1721
SD cells Bladder Homo sapiens (Human) CVCL_W902
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
JO'N cells Urinary bladder Homo sapiens (Human) CVCL_M891
JMSU-1 cells Ascites Homo sapiens (Human) CVCL_2081
HT1197 cells Urinary bladder Homo sapiens (Human) CVCL_1291
DSH1 cells Urinary bladder Homo sapiens (Human) CVCL_1182
CAL-29 cells Urinary bladder Homo sapiens (Human) CVCL_1808
BFTC-905 cells Urinary bladder Homo sapiens (Human) CVCL_1083
BC-3C cells Urinary bladder Homo sapiens (Human) CVCL_1958
97-7 cells Bladder Homo sapiens (Human) CVCL_8625
97-24 cells Bladder Homo sapiens (Human) CVCL_8621
97-18 cells Bladder Homo sapiens (Human) CVCL_8619
97-1 cells Bladder Homo sapiens (Human) CVCL_8616
96-1 cells Bladder Homo sapiens (Human) CVCL_8609
94-10 cells Bladder Homo sapiens (Human) CVCL_8608
647V cells Urinary bladder Homo sapiens (Human) CVCL_1049
253J cells Lymph node Homo sapiens (Human) CVCL_7935/CVCL_7938
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Disease Class: Bladder cancer [20]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Resistant Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.S653C (c.1958C>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
T24 cells Bladder Homo sapiens (Human) CVCL_0554
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
HT1376 cells Bladder Homo sapiens (Human) CVCL_1292
RT112 cells Bladder Homo sapiens (Human) CVCL_1670
TCCSuP cells Bladder Homo sapiens (Human) CVCL_1738
UM-UC3 cells Urinary bladder Homo sapiens (Human) CVCL_1783
WH cells Bladder Homo sapiens (Human) CVCL_0C39
VM-CUBIII cells Urinary bladder Homo sapiens (Human) CVCL_9830
VM-CUBII cells Urinary bladder Homo sapiens (Human) CVCL_9829
VM-CUBI cells Obturator lymph node Homo sapiens (Human) CVCL_1786
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
TSU-PR1 cells Urinary bladder Homo sapiens (Human) CVCL_4014
SW1710 cells Bladder Homo sapiens (Human) CVCL_1721
SD cells Bladder Homo sapiens (Human) CVCL_W902
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
JO'N cells Urinary bladder Homo sapiens (Human) CVCL_M891
JMSU-1 cells Ascites Homo sapiens (Human) CVCL_2081
HT1197 cells Urinary bladder Homo sapiens (Human) CVCL_1291
DSH1 cells Urinary bladder Homo sapiens (Human) CVCL_1182
CAL-29 cells Urinary bladder Homo sapiens (Human) CVCL_1808
BFTC-905 cells Urinary bladder Homo sapiens (Human) CVCL_1083
BC-3C cells Urinary bladder Homo sapiens (Human) CVCL_1958
97-7 cells Bladder Homo sapiens (Human) CVCL_8625
97-24 cells Bladder Homo sapiens (Human) CVCL_8621
97-18 cells Bladder Homo sapiens (Human) CVCL_8619
97-1 cells Bladder Homo sapiens (Human) CVCL_8616
96-1 cells Bladder Homo sapiens (Human) CVCL_8609
94-10 cells Bladder Homo sapiens (Human) CVCL_8608
647V cells Urinary bladder Homo sapiens (Human) CVCL_1049
253J cells Lymph node Homo sapiens (Human) CVCL_7935/CVCL_7938
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Afabicin
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 [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Afabicin
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Afabicin
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Afabicin
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
AUY922
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 [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug AUY922
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug AUY922
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug AUY922
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)/p.A775_G776insYVMA + p.C805S
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Poziotinib
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 Poziotinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
CUTO14 cells N.A. . N.A.
In Vivo Model Female nu/nu nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell Titer Glo assay
Mechanism Description The duplication p.Y772_A775 (c.2314_2325) in gene ERBB2 cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.
Disease Class: Solid tumour/cancer [21]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
CUTO14 cells N.A. . N.A.
In Vivo Model Female nu/nu nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell Titer Glo assay
Mechanism Description The duplication p.Y772_A775 (c.2314_2325) in gene ERBB2 cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.
Disease Class: Solid tumour/cancer [21]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVV (c.2326_2328delinsGTAGTA)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
CUTO14 cells N.A. . N.A.
In Vivo Model Female nu/nu nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell Titer Glo assay
Mechanism Description The complex-indel p.G776_776delinsVV (c.2326_2328delinsGTAGTA) in gene ERBB2 cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.
Disease Class: Solid tumour/cancer [21]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
CUTO14 cells N.A. . N.A.
In Vivo Model Female nu/nu nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell Titer Glo assay
Mechanism Description The complex-indel p.G776_776delinsVC (c.2326_2328delinsGTATGT) in gene ERBB2 cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.
Disease Class: Solid tumour/cancer [21]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
CUTO14 cells N.A. . N.A.
In Vivo Model Female nu/nu nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cell Titer Glo assay
Mechanism Description The duplication p.G778_P780 (c.2332_2340) in gene ERBB2 cause the sensitivity of Poziotinib by aberration of the drug's therapeutic target.
Disease Class: Lung adenocarcinoma [5]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Lung adenocarcinoma [22]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Identified from the Human Clinical Data
Disease Class: Lung adenocarcinoma [22]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Identified from the Human Clinical Data
Disease Class: Lung adenocarcinoma [22]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Missense mutation
p.E812K (c.2434G>A)
Experimental Note Identified from the Human Clinical Data
Disease Class: Lung adenocarcinoma [5]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Poziotinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Sapitinib
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: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.L869R (c.2606T>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.L755S (c.2263_2264delCTinsAG)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.L755P (c.2264T>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.D769N (c.2305G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.D769H (c.2305G>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.D769Y (c.2305G>T)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.V773M (c.2317G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsLC (c.2326_2328delinsCTTTGT)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVV (c.2326_2328delinsGTAGTA)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.V777L (c.2329G>C)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration IF-insertion
p.G778_S779insLPS (c.2334_2335insCTTCCTAGC)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.L786V (c.2356C>G)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
Disease Class: Solid tumour/cancer [23]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Sapitinib
 Drug Info 
Molecule Alteration Missense mutation
p.V842I (c.2524G>A)
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
CW-2 cells Colon Homo sapiens (Human) CVCL_1151
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model NOD.Cg-Prkdcscid IL2rtftmWjl/Szj xenograft model Mus musculus
Experiment for
Drug Resistance		 Cell Titer Glo assay
AEE-788
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: Solid tumour/cancer [24]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AEE-788
 Drug Info 
Molecule Alteration Missense mutation
p.L755S (c.2263_2264delCTinsAG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.L755S (c.2263_2264delCTinsAG) in gene ERBB2 cause the resistance of AEE-788 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AEE-788
 Drug Info 
Molecule Alteration Missense mutation
p.L755P (c.2264T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.L755P (c.2264T>C) in gene ERBB2 cause the resistance of AEE-788 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AEE-788
 Drug Info 
Molecule Alteration Missense mutation
p.T798M (c.2393_2394delCAinsTG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the resistance of AEE-788 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: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug AEE-788
 Drug Info 
Molecule Alteration Missense mutation
p.V773A (c.2318T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.V773A (c.2318T>C) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug AEE-788
 Drug Info 
Molecule Alteration Missense mutation
p.V777L (c.2329G>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.V777L (c.2329G>C) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug AEE-788
 Drug Info 
Molecule Alteration Missense mutation
p.N857S (c.2570A>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.N857S (c.2570A>G) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug AEE-788
 Drug Info 
Molecule Alteration Missense mutation
p.T862A (c.2584A>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.T862A (c.2584A>G) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug AEE-788
 Drug Info 
Molecule Alteration Missense mutation
p.H878Y (c.2632C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.H878Y (c.2632C>T) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target
Pyrotinib
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: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Pyrotinib
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Pyrotinib
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Pyrotinib
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
Discontinued Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Rociletinib
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: Non-small cell lung cancer [25], [26]
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Resistant Drug Rociletinib
 Drug Info 
Molecule Alteration Structural variation
Copy number gain
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Next-generation sequencing analysis; Gene copy number analysis
Experiment for
Drug Resistance		 Progression-free survival assay
Mechanism Description Similarly,resistance to the third-generation inhibitor rociletinib may not only be mediated by EGFR (L798I, C797S) mutations, but also by alterations of MET, PIk3CA, ERRB2, and kRAS, and by the negative selection of T790M-mutant subclones.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Non-small cell lung cancer [25]
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Resistant Drug Rociletinib
 Drug Info 
Molecule Alteration Structural variation
Amplification
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Circulating tumour DNA (ctDNA) analysis
Experiment for
Drug Resistance		 Tissue biopsy assay; CT scan assay
Mechanism Description Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses.
Preclinical Drug(s)
6 drug(s) in total
Click to Show/Hide the Full List of Drugs
AZ5104
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: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AZ5104
 Drug Info 
Molecule Alteration Duplication
p.Y772_A775 (c.2314_2325)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Solid tumour/cancer [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AZ5104
 Drug Info 
Molecule Alteration Duplication
p.G778_P780 (c.2332_2340)
Experimental Note Identified from the Human Clinical Data
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug AZ5104
 Drug Info 
Molecule Alteration Complex-indel
p.G776_776delinsVC (c.2326_2328delinsGTATGT)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Sanger cDNA sequencing assay
Experiment for
Drug Resistance		 CCK-8 assay
EKI-285
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: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug EKI-285
 Drug Info 
Molecule Alteration Missense mutation
p.T798M (c.2393_2394delCAinsTG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug EKI-285
 Drug Info 
Molecule Alteration Missense mutation
p.L755S (c.2263_2264delCTinsAG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.L755S (c.2263_2264delCTinsAG) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug EKI-285
 Drug Info 
Molecule Alteration Missense mutation
p.L755P (c.2264T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.L755P (c.2264T>C) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target
ERBB2 TKIs
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: Solid tumour/cancer [27]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ERBB2 TKIs
 Drug Info 
Molecule Alteration Missense mutation
p.G309E (c.926G>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
Experiment for
Drug Resistance		 WST-1 assay
Mechanism Description The missense mutation p.G309E (c.926G>A) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [27]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ERBB2 TKIs
 Drug Info 
Molecule Alteration Missense mutation
p.S310Y (c.929C>A)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
Experiment for
Drug Resistance		 WST-1 assay
Mechanism Description The missense mutation p.S310Y (c.929C>A) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [27]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ERBB2 TKIs
 Drug Info 
Molecule Alteration Missense mutation
p.S310F (c.929C>T)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
Experiment for
Drug Resistance		 WST-1 assay
Mechanism Description The missense mutation p.S310F (c.929C>T) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [27]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ERBB2 TKIs
 Drug Info 
Molecule Alteration Missense mutation
p.C311R (c.931T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
Experiment for
Drug Resistance		 WST-1 assay
Mechanism Description The missense mutation p.C311R (c.931T>C) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [27]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ERBB2 TKIs
 Drug Info 
Molecule Alteration Missense mutation
p.E321G (c.962A>G)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
Experiment for
Drug Resistance		 WST-1 assay
Mechanism Description The missense mutation p.E321G (c.962A>G) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target
JQ1/Osimertinib
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: Solid tumour/cancer [28]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug JQ1/Osimertinib
 Drug Info 
Molecule Alteration IF-insertion
p.Y772_A775dupYVMA (c.2325_2326insTATGTAATGGCA)
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NCI-H1781 cells Pleural effusion Homo sapiens (Human) CVCL_1494
Experiment for
Molecule Alteration		 Western blotting analysis; Immunohistochemistry; H&E staining assay
Experiment for
Drug Resistance		 CCK-8 assay
Pilaralisib
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 [12]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Sensitive Drug Pilaralisib
 Drug Info 
Molecule Alteration Missense mutation
p.T798M (c.2393_2394delCAinsTG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model BT474 cells Breast Homo sapiens (Human) CVCL_0179
MCF10A cells Breast Homo sapiens (Human) CVCL_0598
In Vivo Model Athymic female mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 HER2T798M sequencing assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the sensitivity of Pilaralisib by aberration of the drug's therapeutic target
WZ4002
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: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug WZ4002
 Drug Info 
Molecule Alteration Missense mutation
p.L755S (c.2263_2264delCTinsAG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.L755S (c.2263_2264delCTinsAG) in gene ERBB2 cause the sensitivity of WZ4002 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug WZ4002
 Drug Info 
Molecule Alteration Missense mutation
p.L755P (c.2264T>C)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.L755P (c.2264T>C) in gene ERBB2 cause the sensitivity of WZ4002 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [24]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug WZ4002
 Drug Info 
Molecule Alteration Missense mutation
p.T798M (c.2393_2394delCAinsTG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the sensitivity of WZ4002 by aberration of the drug's therapeutic target
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
CI-1040
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: Breast adenocarcinoma [12]
Resistant Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Resistant Drug CI-1040
 Drug Info 
Molecule Alteration Missense mutation
p.T798M (c.2393_2394delCAinsTG)
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model BT474 cells Breast Homo sapiens (Human) CVCL_0179
MCF10A cells Breast Homo sapiens (Human) CVCL_0598
In Vivo Model Athymic female mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 HER2T798M sequencing assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the resistance of CI-1040 by aberration of the drug's therapeutic target
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
Click to Show/Hide the Resistance Disease of This Class
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: 2.78E-03; Fold-change: 5.85E-01; Z-score: 4.11E+00
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 1.49E-08; Fold-change: 2.05E-01; Z-score: 8.91E-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
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: 7.14E-04; Fold-change: -1.26E-01; Z-score: -1.91E-01
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 3.52E-03; Fold-change: -1.10E-01; Z-score: -1.40E-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
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: 3.50E-77; Fold-change: 4.91E-01; Z-score: 1.12E+00
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 6.69E-13; Fold-change: 3.54E-01; Z-score: 6.25E-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
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: 5.67E-03; Fold-change: -1.26E+00; Z-score: -2.05E+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
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: 3.48E-14; Fold-change: -6.47E-01; Z-score: -7.78E-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
Tissue-specific Molecule Abundances in Healthy Individuals
Click to Show/Hide the Molecule Abundances
Download the Tissue-Specific Variation(s) Profile
References
Ref 1 Heterogeneity of Acquired Resistance to Anti-EGFR Monoclonal Antibodies in Patients with Metastatic Colorectal Cancer. Clin Cancer Res. 2017 May 15;23(10):2414-2422. doi: 10.1158/1078-0432.CCR-16-1863. Epub 2016 Oct 25.
Ref 2 Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution. Cancer Discov. 2014 Nov;4(11):1269-80. doi: 10.1158/2159-8290.CD-14-0462. Epub 2014 Oct 7.
Ref 3 MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2). Med Sci Monit. 2018 Aug 27;24:5960-5972. doi: 10.12659/MSM.909458.
Ref 4 The functional mechanism of miR-125b in gastric cancer and its effect on the chemosensitivity of cisplatin. Oncotarget. 2017 Dec 14;9(2):2105-2119. doi: 10.18632/oncotarget.23249. eCollection 2018 Jan 5.
Ref 5 Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro studyLung Cancer. 2018 Dec;126:72-79. doi: 10.1016/j.lungcan.2018.10.019. Epub 2018 Oct 17.
Ref 6 Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 InhibitorsCancer Res. 2017 May 15;77(10):2712-2721. doi: 10.1158/0008-5472.CAN-16-3404. Epub 2017 Mar 31.
Ref 7 Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumorsAnn Oncol. 2015 Jul;26(7):1421-7. doi: 10.1093/annonc/mdv186. Epub 2015 Apr 21.
Ref 8 MiR-1268b confers chemosensitivity in breast cancer by targeting ERBB2-mediated PI3K-AKT pathway. Oncotarget. 2017 Aug 9;8(52):89631-89642. doi: 10.18632/oncotarget.20099. eCollection 2017 Oct 27.
Ref 9 miR-125b acts as a tumor suppressor in chondrosarcoma cells by the sensitization to doxorubicin through direct targeting the ErbB2-regulated glucose metabolism. Drug Des Devel Ther. 2016 Feb 24;10:571-83. doi: 10.2147/DDDT.S90530. eCollection 2016.
Ref 10 Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat Rev Clin Oncol. 2014 Aug;11(8):473-81. doi: 10.1038/nrclinonc.2014.104. Epub 2014 Jul 1.
Ref 11 HER2 Reactivation through Acquisition of the HER2 L755S Mutation as a Mechanism of Acquired Resistance to HER2-targeted Therapy in HER2(+) Breast CancerClin Cancer Res. 2017 Sep 1;23(17):5123-5134. doi: 10.1158/1078-0432.CCR-16-2191. Epub 2017 May 9.
Ref 12 Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2Clin Cancer Res. 2013 Oct 1;19(19):5390-401. doi: 10.1158/1078-0432.CCR-13-1038. Epub 2013 Aug 15.
Ref 13 Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) Drives Proliferation of IPH-926 lobular Carcinoma Cells. PLoS One. 2015 Aug 28;10(8):e0136845. doi: 10.1371/journal.pone.0136845. eCollection 2015.
Ref 14 HER kinase inhibition in patients with HER2- and HER3-mutant cancersNature. 2018 Feb 8;554(7691):189-194. doi: 10.1038/nature25475. Epub 2018 Jan 31.
Ref 15 Post-transcriptional regulation of ERBB2 by miR26a/b and HuR confers resistance to tamoxifen in estrogen receptor-positive breast cancer cells. J Biol Chem. 2017 Aug 18;292(33):13551-13564. doi: 10.1074/jbc.M117.780973. Epub 2017 Jun 21.
Ref 16 Activation of LncRNA TINCR by H3K27 acetylation promotes Trastuzumab resistance and epithelial-mesenchymal transition by targeting MicroRNA-125b in breast Cancer. Mol Cancer. 2019 Jan 8;18(1):3. doi: 10.1186/s12943-018-0931-9.
Ref 17 Involvement of miR-770-5p in trastuzumab response in HER2 positive breast cancer cells. PLoS One. 2019 Apr 22;14(4):e0215894. doi: 10.1371/journal.pone.0215894. eCollection 2019.
Ref 18 Targeted therapy with trastuzumab for advanced salivary ductal carcinoma: case report and literature reviewMed Oncol. 2012 Jun;29(2):704-6. doi: 10.1007/s12032-011-9884-1. Epub 2011 Mar 6.
Ref 19 HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancerN Engl J Med. 2006 Jun 15;354(24):2619-21. doi: 10.1056/NEJMc060020.
Ref 20 Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinibCancer Biol Ther. 2014 Sep;15(9):1239-47. doi: 10.4161/cbt.29687. Epub 2014 Jul 14.
Ref 21 Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancerNat Med. 2018 May;24(5):638-646. doi: 10.1038/s41591-018-0007-9. Epub 2018 Apr 23.
Ref 22 Clinical Activity of Pan-HER Inhibitors Against HER2-Mutant Lung AdenocarcinomaClin Lung Cancer. 2018 Sep;19(5):e775-e781. doi: 10.1016/j.cllc.2018.05.018. Epub 2018 Jun 5.
Ref 23 Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 ActivityCancer Cell. 2019 Oct 14;36(4):444-457.e7. doi: 10.1016/j.ccell.2019.09.001. Epub 2019 Oct 3.
Ref 24 Differential sensitivity of ERBB2 kinase domain mutations towards lapatinibPLoS One. 2011;6(10):e26760. doi: 10.1371/journal.pone.0026760. Epub 2011 Oct 28.
Ref 25 Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients. Nat Commun. 2016 Jun 10;7:11815. doi: 10.1038/ncomms11815.
Ref 26 Tumor Evolution as a Therapeutic Target. Cancer Discov. 2017 Jul 20. doi: 10.1158/2159-8290.CD-17-0343. Online ahead of print.
Ref 27 Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14476-81. doi: 10.1073/pnas.1203201109. Epub 2012 Aug 20.
Ref 28 Targeting HER2 Aberrations in Non-Small Cell Lung Cancer with OsimertinibClin Cancer Res. 2018 Jun 1;24(11):2594-2604. doi: 10.1158/1078-0432.CCR-17-1875. Epub 2018 Jan 3.

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