Molecular Profile Detail

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Profile Name FBXW7 R505C
Gene Variant Detail

FBXW7 R505C (loss of function)

Relevant Treatment Approaches mTORC1 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
FBXW7 R505C T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R505C conferred resistance to gamma secretase inhibitor, MRK-003, by activation of the NOTCH pathway and stablization of MYC as demonstrated in T cell acute lymphoblastic leukemia (T-ALL) cell lines (PMID: 17646409). 17646409
FBXW7 R505C head and neck squamous cell carcinoma sensitive Vorinostat Preclinical Actionable In a preclinical study, Zolinza (vorinostat) inhibited growth of a head and neck squamous cell carcinoma cell line harboring FBXW7 R505C in culture (PMID: 23274910). 23274910
FBXW7 R505C colorectal cancer resistant Regorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cell lines with FBXW7 R505C demonstrated acquired resistance in regorafenib (PMID: 27399335). 27399335
FBXW7 R505C melanoma predicted - resistant unspecified PD-1 antibody Preclinical Actionable In a preclinical study, a melanoma cell line expressing FBXW7 R505C in a mouse model conferred resistance to treatment with an unspecified PD-1 antibody, demonstrating increased tumor volume and decreased survival compared to models with wild-type FBXW7 (PMID: 32371478). 32371478
FBXW7 R505C melanoma predicted - resistant Pembrolizumab Case Reports/Case Series Actionable In a clinical case study, a melanoma patient treated with Keytruda (pembrolizumab) demonstrated a response in all lesions except one, which was found to harbor FBXW7 R505C (PMID: 32371478). 32371478