Molecular Profile Detail

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
KRAS G12C lung adenocarcinoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12C mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12C non-small cell lung carcinoma sensitive RAS Inhibitor (Pan) CID1067700 Preclinical Actionable In a preclinical study, CID1067700 inhibited growth and increased apoptosis of non-small cell lung cancer cells that harbor KRAS G12C in culture (PMID: 26247207, PMID: 19477428). 26247207 19477428
KRAS G12C Advanced Solid Tumor sensitive ARS-853 Preclinical Actionable In a preclinical study, ARS-853 inhibited growth of several human tumor cell lines harboring KRAS G12C in 3-dimensional culture conditions (PMID: 26739882). 26739882
KRAS G12C lung cancer sensitive AZD4785 AZD4785 Preclinical - Pdx Actionable In a preclinical study, AZD4785 inhibited Kras expression and downstream signaling, resulted in tumor growth inhibition in patient-derived xenograft models of lung cancer harboring KRAS G12C (PMID: 28615361). 28615361
KRAS G12C pancreatic cancer sensitive RMC-4550 Preclinical - Cell line xenograft Actionable In a preclinical study, RMC-4550 decreased RAS-GTP level, inhibited Erk phosphorylation and proliferation of pancreatic cancer cells harboring KRAS G12C in culture, resulted in dose-dependent tumor growth inhibition in cell line xenograft models (PMID: 30104724). 30104724
KRAS G12C pancreatic ductal adenocarcinoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical - Cell culture Actionable In a preclinical study, pancreatic ductal adenocarcinoma cells harboring KRAS G12C demonstrated reduced sensitivity to Selumetinib (AZD6244) in culture when compared to the combined therapy of Selumetinib (AZD6244) and SHP099 (PMID: 30045908). 30045908
KRAS G12C lung adenocarcinoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12C mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12C non-small cell lung carcinoma sensitive Sorafenib Phase II Actionable In a Phase II trial, treatment with Nexavar (sorafenib) resulted in partial response (PR) in 8.8% (5/57) and stable disease (SD) in 43.8% (25/57) of patients with KRAS-mutant non-small cell lung cancer, including SD in 12 patients and PR in 3 patients with KRAS G12C (PMID: 23224737). 23224737
KRAS G12C pancreatic cancer sensitive MEK inhibitor (Pan) GDC-0623 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC-0623 induced tumor regression in pancreatic cancer cell line xenograft models harboring KRAS G12C (PMID: 23934108). 23934108
KRAS G12C pancreatic adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, a pancreatic adenocarcinoma cell line harboring KRAS G12C demonstrated sensitivity to growth inhibition by MEK inhibitors, including PD-0325901, in culture (PMID: 28957417). 28957417
KRAS G12C non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human lung cells harboring KRAS G12C in culture (PMID: 25665005). 25665005
KRAS G12C lung cancer sensitive RMC-4550 Preclinical - Cell line xenograft Actionable In a preclinical study, RMC-4550 decreased RAS-GTP level, inhibited Erk phosphorylation and proliferation of lung cancer cell lines harboring KRAS G12C in culture, resulted in dose-dependent tumor growth inhibition in cell line xenograft models (PMID: 30104724). 30104724
KRAS G12C pancreatic adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BI-847325 Preclinical - Cell line xenograft Actionable In a preclinical study, BI-847325 induced sustained tumor regression in pancreatic adenocarcinoma cell line xenograft models harboring KRAS G12C (PMID: 27496137). 27496137
KRAS G12C pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Selumetinib (AZD6244) and SHP099 resulted in a synergistic effect, demonstrating reduced cell proliferation and decreased colony formation in pancreatic ductal adenocarcinoma cells harboring KRAS G12C (PMID: 30045908). 30045908
KRAS G12C pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor SHP099 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Mekinist (trametinib) and SHP099 led to reduced cell viability in pancreatic ductal adenocarcinoma cells harboring KRAS G12C in culture (PMID: 30045908). 30045908
KRAS G12C colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring KRAS G12C in culture (PMID: 28179366). 28179366
KRAS G12C esophageal cancer predicted - sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited growth of esophageal cancer cells harboring KRAS G12C in 3D culture (PMID: 30104724). 30104724
KRAS G12C non-small cell lung carcinoma sensitive AZD4785 AZD4785 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD4785 inhibited Kras expression, resulted in growth inhibition in 3-D cultures of non-small cell lung carcinoma cell lines harboring KRAS G12C, and anti-tumor activity in cell line xenograft models (PMID: 28615361). 28615361
KRAS G12C pancreatic cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) inhibited tumor growth in xenograft models of a human pancreatic cancer cell line harboring KRAS G12C (PMID: 23934108). 23934108
KRAS G12C colorectal cancer resistant Sunitinib Preclinical Actionable In a preclinical study, a colorectal cancer cell line harboring the KRAS G12C mutation showed resistance to Sutent (sunitinib) treatment (PMID: 23455880). 23455880
KRAS G12C pancreatic adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Refametinib Preclinical - Cell culture Actionable In a preclinical study, a pancreatic adenocarcinoma cell line harboring KRAS G12C demonstrated sensitivity to growth inhibition by MEK inhibitors, including Refametinib (BAY86-9766), in culture (PMID: 28957417). 28957417
KRAS G12C lung adenocarcinoma sensitive Afatinib Preclinical - Pdx Actionable In a preclinical study, a lung adenocarcinoma patient-derived xenograft (PDX) model was sensitive to treatment with Gilotrif (afatinib), demonstrating inhibition of tumor growth (PMID: 29925635). 29925635
KRAS G12C non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) inhibited tumor growth in xenograft models of a human non-small cell lung cancer cell line harboring KRAS G12C (PMID: 23934108). 23934108
KRAS G12C non-small cell lung carcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Docetaxel + Trametinib Phase I Actionable In a Phase I/Ib trial, the subgroup of non-small cell lung cancer patients harboring KRAS G12C demonstrated a disease control rate (DCR) of 80% (8/10; 4 partial responses, 4 stable disease) following treatment with the combination of Mekinist (trametinib) and Taxotere (docetaxel), compared to a DCR of 60% (15/25) in the overall KRAS-mutant population (PMID: 27876675). 27876675
KRAS G12C pancreatic adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical - Cell culture Actionable In a preclinical study, a pancreatic adenocarcinoma cell line harboring KRAS G12C demonstrated sensitivity to growth inhibition by Selumetinib (AZD6244) in culture (PMID: 28957417). 28957417
KRAS G12C non-small cell lung carcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib + Docetaxel Phase I Actionable In a Phase I study, NSCLC patients harboring KRAS G12C or G12V mutations demonstrated a trend towards better overall survival, progression free survival, and objective response rate compared to NSCLC patients with other KRAS mutations when treated with the combination therapy, Selumetinib (AZD6244) and Taxotere (docetaxel) (PMID: 26125448). 26125448
KRAS G12C non-small cell lung carcinoma sensitive RAS Inhibitor (Pan) SML-10-70-1 Preclinical - Cell culture Actionable In a preclinical study, SML-10-70-1 inhibited proliferation and Erk/Akt signaling in non-small cell lung cancer cells expressing KRAS G12C in culture (PMID: 24259466). 24259466
KRAS G12C pancreatic cancer sensitive Ulixertinib Preclinical - Cell line xenograft Actionable In a preclinical study, Ulixertinib (BVD-523) inhibited Erk signaling in pancreatic cancer cells harboring KRAS G12C, resulted in cell cycle arrest in culture and tumor growth inhibition in cell line xenograft models (PMID: 28939558). 28939558
KRAS G12C non-small cell lung carcinoma sensitive ARS-853 Preclinical - Cell culture Actionable In a preclinical study, ARS-853 treatment in culture resulted in decreased cell proliferation and apoptotic induction in non-small cell lung carcinoma cells harboring KRAS G12C (PMID: 26841430). 26841430
KRAS G12C pancreatic cancer sensitive PI3K Inhibitor (Pan) Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human pancreatic cancer cell lines harboring KRAS G12C in culture (PMID: 21325073, PMID: 12068308). 21325073 12068308
KRAS G12C non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Navitoclax Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring KRAS G12C in culture (PMID: 25665005). 25665005
KRAS G12C non-small cell lung carcinoma sensitive RMC-4550 Preclinical - Pdx Actionable In a preclinical study, RMC-4550 treatment resulted in decreased Erk phosphorylation and dose-dependent tumor growth inhibition in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring KRAS G12C (PMID: 30104724). 30104724
KRAS G12C lung cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor SCH772984 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and SCH772984 combination treatment demonstrated enhanced growth inhibition and sustained inhibition of Erk signaling in lung cancer cells harboring KRAS G12C in culture (PMID: 27338794). 27338794
KRAS G12C pancreatic adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, a pancreatic adenocarcinoma cell line harboring KRAS G12C demonstrated sensitivity to growth inhibition by MEK inhibitors, including Mekinist (trametinib), in culture (PMID: 28957417). 28957417
KRAS G12C non-small cell lung carcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor GLPG0634 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring KRAS G12C in culture that had, over time, acquired resistance to Selumetinib (AZD6244) showed decreased drug resistance when treatment was combined with Filgotinib (GLPG0634), demonstrating reduced expression of Osmr and phosphorylated-Stat3, and decreased cell viability (PMID: 28729401). 28729401
KRAS G12C rectum cancer predicted - sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited growth of rectal cancer cells harboring KRAS G12C in 3D culture (PMID: 30104724). 30104724
Clinical Trial Phase Therapies Title Recruitment Status
NCT03785249 Phase Ib/II MRTX849 MRTX849 in Patients With Cancer Having a KRAS G12C Mutation Recruiting