Molecular Profile Detail

Profile Name KRAS act mut
Gene Variant Detail

KRAS act mut (gain of function)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
KRAS act mut colorectal cancer predicted - sensitive VX-11e + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e sensitized colorectal cancer cell lines harboring KRAS or BRAF activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
KRAS act mut lung cancer predicted - sensitive Dinaciclib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cell lines harboring activating KRAS mutations demonstrated increased sensitivity to Dinaciclib (SCH 727965) in culture (PMID: 27550941). 27550941
KRAS act mut ovarian cancer predicted - sensitive PD-0325901 + Gedatolisib Phase I Actionable In a Phase I trial, treatment with the combination of Gedatolisib (PF-05212384) and PD-0325901 resulted in an overall response rate of 11.1% (4/44) and clinical benefit rate of 16.3% (7/44) in patients with a variety of solid tumors, with responses seen in 3 patients with KRAS-mutant ovarian cancer and 1 patient with KRAS-mutant endometrial cancer (PMID: 29067643). 29067643
KRAS act mut non-small cell lung carcinoma sensitive RAF709 Preclinical - Pdx Actionable In a preclinical study, RAF709 inhibited tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring KRAS activating mutations (PMID: 29343524). 29343524
KRAS act mut colorectal cancer no benefit Venetoclax + VX-11e Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e did not sensitize colorectal cancer cell lines harboring KRAS or BRAF activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). 27974663
KRAS act mut colorectal cancer sensitive AZ628 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) and AZ628 synergistically inhibited Mapk signaling and cell proliferation in colorectal cancer cell lines harboring KRAS activating mutations in culture (PMID: 26351322). 26351322
Clinical Trial Phase Therapies Title Recruitment Status
NCT03155620 Phase II Tazemetostat Larotrectinib LY3023414 Vemurafenib Olaparib Selumetinib Ensartinib Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Advanced Refractory Solid Tumors or Lymphomas Recruiting
NCT03310541 Phase I Capivasertib AZD5363 + Enzalutamide AZD5363 + Fulvestrant AZD5363 in Patients With Advanced Solid Tumors Harboring AKT Mutations Recruiting
NCT03114319 Phase I TNO155 Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors Recruiting
NCT02974803 Phase II Trametinib + Dabrafenib Concurrent Dabrafenib and Trametinib With Sterotactic Radiation in Patients With BRAF Mutation-Positive Malignant Melanoma and Brain Metastases Recruiting