Molecular Profile Detail

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Profile Name FBXW7 W425R
Gene Variant Detail

FBXW7 W425R (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 R465H lung adenocarcinoma sensitive mTORC1 Inhibitor 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 H468R adult T-cell leukemia resistant JQ1 Preclinical - Cell culture Actionable In a preclinical study, adult T cell leukemia cells expressing FBXW7 H468R were resistant to treatment with JQ1 in culture (PMID: 32907612). 32907612
FBXW7 H468R adult T-cell leukemia resistant Birabresib Preclinical - Cell culture Actionable In a preclinical study, adult T cell leukemia cells expressing FBXW7 H468R were resistant to treatment with Birabresib (OTX015) in culture (PMID: 32907612). 32907612
FBXW7 S462P adult T-cell leukemia sensitive JQ1 + Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, the combination treatment of JQ1 and Ulixertinib (BVD-523) resulted in greater decreased proliferation of adult T cell leukemia cells expressing FBXW7 S462P when compared to treatment with JQ1 alone in culture (PMID: 32907612). 32907612
FBXW7 S462P adult T-cell leukemia sensitive JQ1 + PLX8394 Preclinical - Cell culture Actionable In a preclinical study, the combination treatment of JQ1 and PLX8394 resulted in greater decreased proliferation of adult T cell leukemia cells expressing FBXW7 S462P when compared to treatment with JQ1 alone in culture (PMID: 32907612). 32907612
FBXW7 S462P adult T-cell leukemia resistant Birabresib Preclinical - Cell culture Actionable In a preclinical study, adult T cell leukemia cells expressing FBXW7 S462P were resistant to treatment with Birabresib (OTX015) in culture (PMID: 32907612). 32907612
FBXW7 S462P adult T-cell leukemia resistant JQ1 Preclinical - Cell culture Actionable In a preclinical study, adult T cell leukemia cells expressing FBXW7 S462P treated with JQ1 demonstrated resistance in both short term and long term culture, and showed increased phosphorylation of Braf, Mek, and Erk, and increased expression of Stat3 and Myc (PMID: 32907612). 32907612
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 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 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 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 loss colon cancer sensitive mTORC1 Inhibitor 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 W425R adult T-cell leukemia resistant Birabresib Preclinical - Cell culture Actionable In a preclinical study, adult T cell leukemia cells expressing FBXW7 W425R demonstrated resistance to treatment with Birabresib (OTX015) in culture (PMID: 32907612). 32907612
FBXW7 W425R adult T-cell leukemia resistant JQ1 Preclinical - Cell culture Actionable In a preclinical study, adult T cell leukemia cells expressing FBXW7 W425R demonstrated resistance to treatment with JQ1 in culture (PMID: 32907612). 32907612
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 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
FBXW7 E192A fibrolamellar carcinoma predicted - sensitive mTORC1 Inhibitor 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 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 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 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 breast cancer sensitive mTORC1 Inhibitor 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 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 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 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 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 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 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 positive adult T-cell leukemia predicted - sensitive JQ1 Preclinical - Cell line xenograft Actionable In a preclinical study, adult T cell leukemia cells expressing FBXW7 in a mouse model demonstrated decreased tumor volume when treated with JQ1 (PMID: 32907612). 32907612
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries