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|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|NOTCH1 act mut||T-cell adult acute lymphocytic leukemia||predicted - sensitive||Dexamethasone + Ribociclib||Preclinical - Pdx||Actionable||In a preclinical study, the combination of Kisqali (ribociclib) and Adexone (dexamethasone) resulted in reduced leukemia burden and a greater survival benefit in a NOTCH1 activated T-cell acute lymphoblastic leukemia patient derived xenograft (PDX) model when compared to control or either agent alone (PMID: 28151717).||28151717|
|NOTCH1 act mut||breast cancer||sensitive||Brontictuzumab||Preclinical - Pdx||Actionable||In a preclinical study, Brontictuzumab (OMP-52M51) inhibited tumor growth and reduced cancer stem cells in xenograft models of tumor derived from a breast cancer patient harboring activating NOTCH1 mutations (Cancer Res 2013;73(8 Suppl):Abstract nr 3728).||detail...|
|NOTCH1 act mut||colorectal cancer||sensitive||PF-03084014||Preclinical - Cell culture||Actionable||In a preclinical study, the gamma secretase inhibitor PF-03084014 reduced Notch1 cleavage, decreased activation of Notch targets, and increased apoptosis in colorectal cancer cell lines exhibiting increased Notch activation (PMID: 23868008).||23868008|
|NOTCH1 act mut||acute lymphoblastic leukemia||sensitive||Brontictuzumab||Preclinical - Pdx||Actionable||In a preclinical study, xenograft models of patient-derived acute lymphocytic leukemia cells harboring NOTCH1 activating muatations demonstrated better response to Brontictuzumab (OMP-52M51) compared to NOTCH1 wild-type models (PMID: 23774673).||23774673|
|NOTCH1 mutant||chronic lymphocytic leukemia||decreased response||Chlorambucil + Ofatumumab||Phase III||Actionable||In a Phase III trial (COMPLEMENT1), the addition of Arzerra (ofatumumab) to Chlorambucil treatment in patients with chronic lymphocytic leukemia was associated with increased benefit to median progression-free survival (mPFS) in patients with wild-type NOTCH1 (mPFS 23.8 mo with ofatumumab vs.13.3 mo without, HR 0.50, CI 95% 0.39-0.63, p<0.01), but did not result in significant mPFS benefit in patients with mutant NOTCH1 (17.2 vs.13.1 mo, HR 0.81, CI 95% 0.50-1.31, p=0.45) (PMID: 31919090; NCT00748189).||31919090|
|NOTCH1 mutant||mantle cell lymphoma||predicted - resistant||Ibrutinib + Venetoclax||Phase II||Actionable||In a Phase II trial (AIM), distinct molecular profiles were identified in mantle cell lymphoma patients responded to Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy compared to those did not respond, with all patients harboring mutations in NSD2 (n=4), UBR5 (n=3), KMT2D (n=3), and 12 of 13 patients harboring mutations in ATM responded to the therapy, while SMARCA4 (n=4), CCND1 (n=2), and NOTCH1 (n=3) alterations were exclusively observed in nonresponders (PMID: 30455436; NCT02471391).||30455436|
|NOTCH1 mutant||triple-receptor negative breast cancer||sensitive||PF-03084014||Preclinical - Pdx||Actionable||In a preclinical study, PF-03084014 treatment resulted in tumor regression in patient-derived xenograft models of triple receptor negative breast cancer harboring NOTCH1 mutations (PMID: 25564152).||25564152|
|Clinical Trial||Phase||Therapies||Title||Recruitment Status|