Molecule Information

General Information of the Molecule (ID: Mol00509)

• Name: MAPK/ERK kinase 1 (MEK1) ,Homo sapiens
• Synonyms: MAP kinase kinase 1; MAPKK 1; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MEK 1; MEK1; PRKMK1
• Molecule Type: Protein
• Gene Name: MAP2K1
• Gene ID: 5604
• Location: chr15:66386837-66491656[+]
• Sequence:
  MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKV
  GELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHE
  CNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYL
  REKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHY
  SVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSY
  GMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAF
  IKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV
• Function: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.
• Uniprot ID: MP2K1_HUMAN
• Ensembl ID: ENSG00000169032
• HGNC ID: HGNC:6840

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

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 5 drug(s) in total

Binimetinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [1]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Binimetinib
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: Phoenix AMPHO cells; Fetal kidney; Homo sapiens (Human); CVCL_H716
• In Vivo Model: NOD scid gamma xenograft model; Mus musculus
• Experiment for Molecule Alteration: Single cell sequencing assay

Regorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Regorafenib
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Regorafenib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Regorafenib
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Regorafenib
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Regorafenib
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Regorafenib
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Regorafenib
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway

Reserpine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Salmonella enterica infection [3]

• Resistant Disease: Salmonella enterica infection [ICD-11: 1A09.0]
• Resistant Drug: Reserpine
• Molecule Alteration: Function; Activation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: T cell receptor signaling pathway; Regulation; hsa04660
• Cell Pathway Regulation: EGFR signaling pathway; Inhibition; hsa01521
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• Cell Pathway Regulation: MEK1/2 signaling pathway; Activation; hsa04010
• In Vivo Model: Chicken ceca explant model; Gallus gallus
• Experiment for Molecule Alteration: Chicken-specific kinome peptide array
• Experiment for Drug Resistance: Bactericidal assays against Salmonella
• Mechanism Description: Reserpine treatment induced T cell activation, reduced CTLA-4 gene expression, and deactivated metabolic pathways like epidermal growth factor receptor (EGFR) signaling and mammalian target of rapamycin (mTOR) signaling, which were linked to antimicrobial responses. MEK1/2 activation plays a central role in reserpine-induced antimicrobial activities.

Temozolomide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Glioma [4]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-181b independently predicted chemoresponse to temozolomide and enhanced temozolomide sensitivity via MEk1 downregulation.

Trametinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Melanoma [5]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Trametinib
• Molecule Alteration: Missense mutation; p.V60E (c.179T>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: A2058 cells; Skin; Homo sapiens (Human); CVCL_1059
• In Vitro Model: WM2664 cells; Skin; Homo sapiens (Human); CVCL_2765
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [6]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Trametinib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SNU-C1 cells; Peritoneum; Homo sapiens (Human); CVCL_1708
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NCI-H226 cells; Pleural effusion; Homo sapiens (Human); CVCL_1544
• In Vitro Model: NCI-H196 cells; Pleural effusion; Homo sapiens (Human); CVCL_1509
• In Vitro Model: NCI-H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• In Vitro Model: NCI-H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC366 cells; Lung; Homo sapiens (Human); CVCL_2059
• In Vitro Model: NCI-H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease Class: Colorectal cancer [6]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Trametinib
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SNU-C1 cells; Peritoneum; Homo sapiens (Human); CVCL_1708
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NCI-H226 cells; Pleural effusion; Homo sapiens (Human); CVCL_1544
• In Vitro Model: NCI-H196 cells; Pleural effusion; Homo sapiens (Human); CVCL_1509
• In Vitro Model: NCI-H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• In Vitro Model: NCI-H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• In Vitro Model: HCC366 cells; Lung; Homo sapiens (Human); CVCL_2059
• In Vitro Model: NCI-H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease Class: Lung adenocarcinoma [6]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Sensitive Drug: Trametinib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SNU-C1 cells; Peritoneum; Homo sapiens (Human); CVCL_1708
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NCI-H226 cells; Pleural effusion; Homo sapiens (Human); CVCL_1544
• In Vitro Model: NCI-H196 cells; Pleural effusion; Homo sapiens (Human); CVCL_1509
• In Vitro Model: NCI-H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• In Vitro Model: NCI-H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC366 cells; Lung; Homo sapiens (Human); CVCL_2059
• In Vitro Model: NCI-H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease Class: Gastric adenocarcinoma [6]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Sensitive Drug: Trametinib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SNU-C1 cells; Peritoneum; Homo sapiens (Human); CVCL_1708
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NCI-H226 cells; Pleural effusion; Homo sapiens (Human); CVCL_1544
• In Vitro Model: NCI-H196 cells; Pleural effusion; Homo sapiens (Human); CVCL_1509
• In Vitro Model: NCI-H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• In Vitro Model: NCI-H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC366 cells; Lung; Homo sapiens (Human); CVCL_2059
• In Vitro Model: NCI-H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lymphatic system cancer [7]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Sensitive Drug: Trametinib
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Skin; .
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Clinical Trial Drug(s) 5 drug(s) in total

Cobimetinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Solid tumour/cancer [1]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Cobimetinib
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH-3T3 cells; Embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: Phoenix AMPHO cells; Fetal kidney; Homo sapiens (Human); CVCL_H716
• In Vivo Model: NOD scid gamma xenograft model; Mus musculus
• Experiment for Molecule Alteration: Single cell sequencing assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Lymphatic system cancer [8]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Sensitive Drug: Cobimetinib
• Molecule Alteration: Missense mutation; p.P124L (c.371C>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole exome sequencing; Targeted Exon Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Disease Class: Lymphatic system cancer [7]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Sensitive Drug: Cobimetinib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Identified from the Human Clinical Data

Disease Class: Lymphatic system cancer [8]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Sensitive Drug: Cobimetinib
• Molecule Alteration: IF-deletion; p.P105_I107delPAI (c.314_322delCCGCAATCC)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole exome sequencing; Targeted Exon Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Disease Class: Lymphatic system cancer [8]

• Sensitive Disease: Lymphatic system cancer [ICD-11: 2E81.1]
• Sensitive Drug: Cobimetinib
• Molecule Alteration: Missense mutation; p.P124Q (c.371C>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole exome sequencing; Targeted Exon Sequencing
• Experiment for Drug Resistance: CellTiter-Glo assay; IC50 assay

Refametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Lung adenocarcinoma [6]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Sensitive Drug: Refametinib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SNU-C1 cells; Peritoneum; Homo sapiens (Human); CVCL_1708
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NCI-H226 cells; Pleural effusion; Homo sapiens (Human); CVCL_1544
• In Vitro Model: NCI-H196 cells; Pleural effusion; Homo sapiens (Human); CVCL_1509
• In Vitro Model: NCI-H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• In Vitro Model: NCI-H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC366 cells; Lung; Homo sapiens (Human); CVCL_2059
• In Vitro Model: NCI-H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Selumetinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Melanoma [9]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target

Disease Class: Melanoma [9]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.I103N (c.308T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.I103N (c.308T>A) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target

Disease Class: Melanoma [9]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.L115P (c.344T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.L115P (c.344T>C) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target

Disease Class: Melanoma [9]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.P124S (c.370C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.P124S (c.370C>T) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target

Disease Class: Melanoma [9]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.P124L (c.371C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.P124L (c.371C>T) in gene MAP2K1 cause the resistance of Selumetinib by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of Selumetinib by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Lung adenocarcinoma [6]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SNU-C1 cells; Peritoneum; Homo sapiens (Human); CVCL_1708
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NCI-H226 cells; Pleural effusion; Homo sapiens (Human); CVCL_1544
• In Vitro Model: NCI-H196 cells; Pleural effusion; Homo sapiens (Human); CVCL_1509
• In Vitro Model: NCI-H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• In Vitro Model: NCI-H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC366 cells; Lung; Homo sapiens (Human); CVCL_2059
• In Vitro Model: NCI-H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease Class: Gastric adenocarcinoma [10]

• Sensitive Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NUGC-4 cells; Lymph node; Homo sapiens (Human); CVCL_3082/CVCL_8372
• Experiment for Molecule Alteration: Multiplex deep sequencing of MAP2K1 cDNAs assay
• Experiment for Drug Resistance: Focus formation assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the sensitivity of Selumetinib by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian cancer [11]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Selumetinib
• Molecule Alteration: IF-deletion; p.Q56_V60delQKQKV (c.166_180del15)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ovary; .
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome analysis
• Experiment for Drug Resistance: Colony formation assay

Disease Class: Lung adenocarcinoma [12]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.K57N (c.171G>T)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue staining assay
• Mechanism Description: The missense mutation p.K57N (c.171G>T) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

Disease Class: Lung adenocarcinoma [12]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Sensitive Drug: Selumetinib
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Trypan blue staining assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the sensitivity of Selumetinib by unusual activation of pro-survival pathway

PD-0325901

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Colorectal cancer [13]

• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: PD-0325901
• Molecule Alteration: Missense mutation; p.F129L
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: RAS/RAF/MEk signaling pathway; Activation; hsa04010
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: HCT-116 MEk-R cells; Colon; Homo sapiens (Human); CVCL_V401
• Experiment for Molecule Alteration: Exome sequencing assay
• Experiment for Drug Resistance: BrdUrd assay
• Mechanism Description: The RAS/RAF/MEk pathway is activated in more than 30% of human cancers, most commonly via mutation in the k-ras oncogene and also via mutations in BRAF. Importantly, in all cases the MEk-resistant cell lines retained their addiction to the mitogen-activated protein kinase (MAPk) pathway, as evidenced by their sensitivity to a selective inhibitor of the ERk1/2 kinases. These data suggest that tumors with acquired MEk inhibitor resistance remain dependent on the MAPk pathway and are therefore sensitive to inhibitors that act downstream of the mutated MEk target.

Disease Class: Breast cancer [13]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: PD-0325901
• Molecule Alteration: Missense mutation; p.L115P
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: RAS/RAF/MEk signaling pathway; Activation; hsa04010
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: HCT-116 MEk-R cells; Colon; Homo sapiens (Human); CVCL_V401
• Experiment for Molecule Alteration: Exome sequencing assay
• Experiment for Drug Resistance: BrdUrd assay
• Mechanism Description: The RAS/RAF/MEk pathway is activated in more than 30% of human cancers, most commonly via mutation in the k-ras oncogene and also via mutations in BRAF. Importantly, in all cases the MEk-resistant cell lines retained their addiction to the mitogen-activated protein kinase (MAPk) pathway, as evidenced by their sensitivity to a selective inhibitor of the ERk1/2 kinases. These data suggest that tumors with acquired MEk inhibitor resistance remain dependent on the MAPk pathway and are therefore sensitive to inhibitors that act downstream of the mutated MEk target.

PLX4720

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Melanoma [9]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: PLX4720
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of PLX4720 by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PLX4720
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PLX4720
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PLX4720
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PLX4720
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PLX4720
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PLX4720
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: PLX4720
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the sensitivity of PLX4720 by unusual activation of pro-survival pathway

Discontinued Drug(s) 1 drug(s) in total

AZD-8330

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-8330
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-8330
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-8330
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-8330
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-8330
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-8330
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: AZD-8330
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of AZD-8330 by unusual activation of pro-survival pathway

Preclinical Drug(s) 3 drug(s) in total

Cetuximab/Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Colorectal cancer [14]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Cetuximab/Trametinib
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: CCK-81 cells; N.A.; Homo sapiens (Human); CVCL_2873

GDC0879

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: GDC0879
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: GDC0879
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: GDC0879
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: GDC0879
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: GDC0879
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: GDC0879
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: GDC0879
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

RO4927350

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Colorectal cancer [15]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: RO4927350
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vivo Model: Mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the sensitivity of RO4927350 by unusual activation of pro-survival pathway

Investigative Drug(s) 4 drug(s) in total

CI-1040

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Melanoma [9]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: CI-1040
• Molecule Alteration: Missense mutation; p.I103N (c.308T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.I103N (c.308T>A) in gene MAP2K1 cause the resistance of CI-1040 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: CI-1040
• Molecule Alteration: Missense mutation; p.I103N (c.308T>A)
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae strain SY2002; 4932
• Experiment for Molecule Alteration: Kinase assay
• Mechanism Description: The missense mutation p.I103N (c.308T>A) in gene MAP2K1 cause the resistance of CI-1040 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: CI-1040
• Molecule Alteration: Missense mutation; p.L115A (c.343_344delCTinsGC)
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae strain SY2002; 4932
• Experiment for Molecule Alteration: Kinase assay
• Mechanism Description: The missense mutation p.L115A (c.343_344delCTinsGC) in gene MAP2K1 cause the resistance of CI-1040 by unusual activation of pro-survival pathway

Disease Class: Melanoma [9]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: CI-1040
• Molecule Alteration: Missense mutation; p.L115P (c.344T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.L115P (c.344T>C) in gene MAP2K1 cause the resistance of CI-1040 by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [16]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: CI-1040
• Molecule Alteration: Missense mutation; p.L115P (c.344T>C)
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae strain SY2002; 4932
• Experiment for Molecule Alteration: Kinase assay
• Mechanism Description: The missense mutation p.L115P (c.344T>C) in gene MAP2K1 cause the resistance of CI-1040 by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [16]

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Sensitive Drug: CI-1040
• Molecule Alteration: Missense mutation; p.F53S (c.158T>C)
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Saccharomyces cerevisiae strain SY2002; 4932
• Experiment for Molecule Alteration: Kinase assay
• Mechanism Description: The missense mutation p.F53S (c.158T>C) in gene MAP2K1 cause the sensitivity of CI-1040 by unusual activation of pro-survival pathway

MEK inhibitors

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Melanoma [9]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.P124L (c.371C>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.P124L (c.371C>T) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.D67N (c.199G>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.D67N (c.199G>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.I99T (c.296T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.I99T (c.296T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.I103N (c.308T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.I103N (c.308T>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.K104N (c.312A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.K104N (c.312A>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.I111N (c.332T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.I111N (c.332T>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.L115P (c.344T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.L115P (c.344T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.H119P (c.356A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.H119P (c.356A>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.E120D (c.360G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.E120D (c.360G>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.G128D (c.383G>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.G128D (c.383G>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.F133L (c.397T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.F133L (c.397T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Disease Class: Solid tumour/cancer [9]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.L215P (c.644T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: The missense mutation p.L215P (c.644T>C) in gene MAP2K1 cause the resistance of MEK inhibitors by aberration of the drug's therapeutic target

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Melanoma [17]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Skin; .
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of MEK inhibitors by unusual activation of pro-survival pathway

Disease Class: Melanoma [18]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: MEK inhibitors
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human melanoma tissue; .
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of MEK inhibitors by unusual activation of pro-survival pathway

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian cancer [11]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: MEK inhibitors
• Molecule Alteration: IF-deletion; p.Q56_V60delQKQKV (c.166_180del15)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ovary; .
• In Vivo Model: Female nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Whole transcriptome analysis
• Experiment for Drug Resistance: Colony formation assay

Panitumumab/Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Colorectal cancer [19]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Panitumumab/Trametinib
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCA46 cells; Colon; Homo sapiens (Human); CVCL_2468
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease Class: Colorectal cancer [19]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Panitumumab/Trametinib
• Molecule Alteration: Missense mutation; p.K57T (c.170A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCA46 cells; Colon; Homo sapiens (Human); CVCL_2468
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Disease Class: Colorectal cancer [19]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Panitumumab/Trametinib
• Molecule Alteration: Missense mutation; p.K57T (c.170A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCA46 cells; Colon; Homo sapiens (Human); CVCL_2468
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

PD98059

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD98059
• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD98059
• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD98059
• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD98059
• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD98059
• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD98059
• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: PD98059
• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of PD98059 by unusual activation of pro-survival pathway

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.08E-99; Fold-change: -1.34E+00; Z-score: -1.74E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.33E-01; Fold-change: 1.15E-01; Z-score: 3.55E-01
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.41E-01; Fold-change: 2.73E-01; Z-score: 5.53E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 9.61E-01; Fold-change: 4.74E-02; Z-score: 2.07E-01

Gastric cancer [ICD-11: 2B72]

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: 4.23E-02; Fold-change: 6.72E-01; Z-score: 2.19E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 7.10E-03; Fold-change: 2.28E-01; Z-score: 6.54E-01

Lung cancer [ICD-11: 2C25]

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: 6.41E-20; Fold-change: 1.95E-01; Z-score: 7.65E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.11E-02; Fold-change: 1.17E-01; Z-score: 2.98E-01

Melanoma [ICD-11: 2C30]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Skin
• The Specified Disease: Melanoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.00E-01; Fold-change: -6.72E-02; Z-score: -1.54E-01

Breast cancer [ICD-11: 2C60]

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: 1.25E-04; Fold-change: -2.21E-01; Z-score: -2.84E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.77E-01; Fold-change: 2.96E-01; Z-score: 3.02E-01

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.61E-02; Fold-change: 6.77E-01; Z-score: 1.31E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 6.55E-03; Fold-change: -4.35E-01; Z-score: -5.88E-01

References

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