Molecular Profile Detail

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Profile Name FBXW7 G437E
Gene Variant Detail

FBXW7 G437E (unknown)

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
FBXW7 del T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, homozygous deletion of FBXW7 is 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 inact mut Advanced Solid Tumor sensitive Entinostat Preclinical Actionable In a preclinical study, entinostat (MS-275) inhibited cancer cells from advanced solid tumors and hematological cells harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut hematologic cancer sensitive AR-42 Preclinical Actionable In a preclinical study, AR-42 inhibited human hematologic cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut breast cancer sensitive Sirolimus Preclinical - Cell line xenograft Actionable In a preclinical study, breast cancer cells harboring a FBXW7 mutation demonstrated sensitivity to Rapamune (sirolimus) in culture and in cell line xenograft models (PMID: 18787170). 18787170
FBXW7 inact mut hematologic cancer sensitive Belinostat Preclinical Actionable In a preclinical study, Beleodaq (belinostat) inhibited human hematologic cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut Advanced Solid Tumor resistant Docetaxel Preclinical Actionable In a preclinical study, human cancer cell lines harboring FBXW7 inactivating mutations were resistant to docetaxel in culture (PMID: 23274910). 23274910
FBXW7 inact mut Advanced Solid Tumor sensitive Belinostat Preclinical Actionable In a preclinical study, Beleodaq (belinostat) inhibited human cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut Advanced Solid Tumor sensitive AR-42 Preclinical Actionable In a preclinical study, AR-42 inhibited human cancer cell lines harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 inact mut hematologic cancer sensitive Entinostat Preclinical Actionable In a preclinical study, entinostat (MS-275) inhibited cancer cells from advanced solid tumors and hematological cells harboring FBXW7 inactivating mutations in culture (PMID: 23274910). 23274910
FBXW7 loss colon cancer sensitive Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) inhibited epithelial-mesenchymal transition, motility, and invasiveness in colon cancer cells lacking FBXW7 in culture (PMID: 23558291) 23558291
FBXW7 loss colon cancer predicted - resistant unspecified PD-1 antibody Preclinical Actionable In a preclinical study, an FBXW7-deficient colon cancer cell line in a mouse model was resistant to treatment with an unspecified PD-1 antibody, demonstrating poor survival and decreased inhibition of tumor growth compared to models with wild-type FBXW7 (PMID: 32371478). 32371478
FBXW7 loss melanoma predicted - resistant unspecified PD-1 antibody Preclinical Actionable In a preclinical study, an FBXW7-deficient melanoma cell line in a mouse model was resistant to treatment with an unspecified PD-1 antibody, demonstrating increased tumor volume and poor survival compared to models with wild-type FBXW7 (PMID: 32371478). 32371478
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 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
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-300, 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 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 W606* NOTCH1 L1600Q NOTCH1 V1721G NOTCH1 S2467fs adenoid cystic carcinoma predicted - resistant Brontictuzumab Case Reports/Case Series Actionable In a clinical case study, FBXW7 W606* and NOTCH1 V1721G were identified at disease progression in a patient with metastatic adenoid cystic carcinoma harboring co-occurring NOTCH1 L1600Q and S2467fs who was treated with Brontictuzumab (OMP-52M51) (PMID: 27870570). 27870570
FBXW7 W606* NOTCH1 L1600Q NOTCH1 V1721G NOTCH1 S2467fs adenoid cystic carcinoma no benefit Sunitinib Case Reports/Case Series Actionable In a clinical case study, Sutent (sunitinib) treatment resulted in rapid disease progression in a patient with metastatic adenoid cystic carcinoma harboring co-occurring NOTCH1 L1600Q and S2467fs, and acquired FBXW7 W606* and NOTCH1 V1721G (PMID: 27870570). 27870570
FBXW7 R505L T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R505L may 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 E192A fibrolamellar carcinoma predicted - sensitive Sirolimus Phase I Actionable In a Phase I study, Rapamune (sirolimus) resulted in prolonged stable disease in a patient with hepatocellular fibrolamellar carcinoma harboring FBXW7 E192A (PMID: 24586741). 24586741
FBXW7 mutant Her2-receptor negative breast cancer predicted - sensitive LY3039478 Phase I Actionable In a Phase I trial, LY3039478 treatment resulted in partial response lasted 9.5 months in a patient with hormone receptor-positive, Erbb2 (Her2)-negative breast cancer harboring FBXW7 mutation (PMID: 30060061; NCT01695005). 30060061
FBXW7 R479Q T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R479Q 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 R465H lung adenocarcinoma sensitive Temsirolimus Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring FBXW7 R465H demonstrated tumor shrinkage when treated with Torisel (temsirolimus) (PMID: 24360397). 24360397
FBXW7 R465H T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R465H 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 R465C T-cell adult acute lymphocytic leukemia resistant MRK-003 Preclinical Actionable In a preclinical study, FBXW7 R465C 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
Clinical Trial Phase Therapies Title Recruitment Status