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Profile Name | FBXW7 R505C |
Gene Variant Detail | |
Relevant Treatment Approaches | mTORC1 Inhibitor |
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 |