Molecular Profile Detail

Profile Name NOTCH1 E1567K
Gene Variant Detail

NOTCH1 E1567K (no effect - predicted)

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
NOTCH1 A1552G osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 A1552G in culture (PMID: 25104330). 25104330
NOTCH1 positive prostate cancer predicted - sensitive PF-03084014 + Docetaxel Preclinical - Cell line xenograft Actionable In a preclinical study, PF-03084014 and Taxotere (docetaxel) in combination inhibited growth of Notch1-expressing Taxotere (docetaxel)-resistant prostate cancer cell lines in culture, and inhibited both soft tissue and bony tumor growth in Taxotere (docetaxel)-resistant prostate cancer cell line xenograft models, with increased efficacy over either agent alone (PMID: 26202948). 26202948
NOTCH1 positive glioblastoma multiforme sensitive Radiotherapy + RO4929097 + Temozolomide Phase I Actionable In a Phase I trial, addition of RO4929097 to Temodar (temozolomide) and radiation therapy inhibited Notch signaling and cell proliferation in patient tumor samples, resulted in a median overall survival of 21 months and a median progression free survival of 13 months in glioblastoma patients (PMID: 27154916). 27154916
NOTCH1 positive breast cancer sensitive LY3039478 Preclinical Actionable In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of breast cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). detail...
NOTCH1 positive glioblastoma multiforme sensitive LY3039478 Preclinical Actionable In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of glioblastoma (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). detail...
NOTCH1 positive stomach cancer sensitive LY3039478 Preclinical Actionable In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of gastric cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). detail...
NOTCH1 positive ovarian cancer sensitive LY3039478 Preclinical Actionable In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of ovarian cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). detail...
NOTCH1 positive colon cancer sensitive LY3039478 Preclinical Actionable In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of colon cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). detail...
NOTCH1 positive lung cancer sensitive LY3039478 Preclinical Actionable In a preclinical study, LY3039478 inhibited Notch1 cleavage and downstream gene expression, demonstrated anti-tumor activity in xenograft models of lung cancer (AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1131). detail...
NOTCH1 V1676I osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 V1676I in culture (PMID: 25104330). 25104330
NOTCH1 I1680S osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 I1680S in culture (PMID: 25104330). 25104330
NOTCH1 rearrange triple-receptor negative breast cancer sensitive MRK-003 + Paclitaxel Preclinical Actionable In a preclinical study, MRK-003 and Taxol (paclitaxel) worked synergistically to inhibit tumor growth in triple receptor-negative breast cancer xenograft models harboring NOTCH1 rearrangement, resulting in tumor regression (PMID: 25104330). 25104330
NOTCH1 rearrange triple-receptor negative breast cancer no benefit MRK-003 + SCH772984 Preclinical Actionable In a preclinical study, SCH772984 did not potentiate the growth inhibition effect of MRK-003 in triple receptor-negative breast cancer cells harboring NOTCH1 rearrangement in culture (PMID: 25104330). 25104330
NOTCH1 rearrange triple-receptor negative breast cancer sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited growth of triple receptor-negative breast cancer cells harboring NOTCH1 rearrangement in culture and reduced tumor growth in xenograft models (PMID: 25104330). 25104330
NOTCH1 A1552V osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 A1552V in culture (PMID: 25104330). 25104330
NOTCH1 V1575A osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 V1575A in culture (PMID: 25104330). 25104330
NOTCH1 act mut acute lymphocytic 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 act mut T-cell adult acute lymphocytic leukemia predicted - sensitive Ribociclib + Dexamethasone 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
EML4-ALK NOTCH1 D1538A non-small cell lung carcinoma predicted - resistant Brigatinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK demonstrated resistance to treatment with Alunbrig (brigatinib), and was subsequently found to have acquired NOTCH1 D1538A (PMID: 29636358). 29636358
ROS1 fusion ERBB2 amp NOTCH1 amp SRC amp STK11 amp non-small cell lung carcinoma predicted - resistant Crizotinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of SRC, ERBB2 (HER2), STK11, and NOTCH1 (PMID: 29636358). 29636358
NOTCH1 A1570G osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 A1570G in culture (PMID: 25104330). 25104330
NOTCH1 C478F head and neck squamous cell carcinoma sensitive LGK974 Preclinical Actionable In a preclinical study, LGK974 inhibited growth of head and neck squamous cell carcinoma cells harboring NOTCH1 C478F in culture and xenograft models (PMID: 24277854). 24277854
NOTCH1 wild-type triple-receptor negative breast cancer no benefit MRK-003 + Paclitaxel Preclinical Actionable In a preclinical study, the combination of MRK-003 and Taxol (paclitaxel) did not potentiate the anti-tumor effects compared to single agent therapy in triple receptor-negative breast cancer xenograft models harboring wild-type NOTCH1 (PMID: 25104330). 25104330
NOTCH1 wild-type triple-receptor negative breast cancer decreased response MRK-003 Preclinical Actionable In a preclinical study, triple receptor-negative breast cancer xenograft models harboring wild-type NOTCH1 demonstrated reduced sensitivity to MRK-003 induced tumor growth inhibition (PMID: 25104330). 25104330
NOTCH1 wild-type RB1 wild-type T-cell adult acute lymphocytic leukemia decreased response Ribociclib + Mercaptopurine Preclinical - Cell culture Actionable In a preclinical study, the addition of Kisqali (ribociclib) to Purixan (mercaptopurine) resulted in an antagonistic effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and wild-type NOTCH1 in culture (PMID: 28151717). 28151717
NOTCH1 wild-type RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib + JQ1 Preclinical - Cell culture Actionable In a preclinical study, the combination of Kisqali (ribociclib) and JQ1 resulted in an additive effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and wild-type NOTCH1 in culture (PMID: 28151717). 28151717
NOTCH1 wild-type RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib Preclinical - Cell culture Actionable In a preclinical study, a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and wild-type NOTCH1 demonstrated sensitivity to treatment with Kisqali (ribociclib) in culture, resulting in inhibition of cell growth (PMID: 28151717). 28151717
NOTCH1 wild-type RB1 wild-type T-cell adult acute lymphocytic leukemia conflicting Ribociclib + Dexamethasone Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Kisqali (ribociclib) and Adexone (dexamethasone) in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and NOTCH1 resulted in decreased cell viability and reduced phosphorylation of Rb1 in culture, however, survival did not differ between xenograft models treated with the combination or Kisqali (ribociclib) alone (PMID: 28151717). 28151717
NOTCH1 wild-type RB1 wild-type T-cell adult acute lymphocytic leukemia decreased response Ribociclib + Methotrexate Preclinical - Cell culture Actionable In a preclinical study, the addition of Kisqali (ribociclib) to Methotrexate resulted in an antagonistic effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and wild-type NOTCH1 in culture (PMID: 28151717). 28151717
NOTCH1 wild-type RB1 wild-type T-cell adult acute lymphocytic leukemia decreased response Ribociclib + Asparaginase Preclinical - Cell culture Actionable In a preclinical study, the addition of Kisqali (ribociclib) to Elspar (asparaginase) resulted in an antagonistic effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and wild-type NOTCH1 in culture (PMID: 28151717). 28151717
NOTCH1 wild-type RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib + Everolimus Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Kisqali (ribociclib) and Afinitor (everolimus) treatment in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and wild-type NOTCH1 resulted in decreased Rb1 phosphorylation and a greater inhibition of cell growth compared to either agent alone in culture, and prolonged survival in cell-line xenograft models (PMID: 28151717). 28151717
NOTCH1 wild-type RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib + Bortezomib Preclinical - Cell culture Actionable In a preclinical study, the combination of Kisqali (ribociclib) and Velcade (bortezomib) resulted in an additive effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and wild-type NOTCH1 in culture (PMID: 28151717). 28151717
NOTCH1 wild-type RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib + Prednisolone Preclinical - Cell culture Actionable In a preclinical study, the combination of Kisqali (ribociclib) and Omnipred (prednisolone) resulted in a synergistic effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and wild-type NOTCH1 in culture (PMID: 28151717). 28151717
NOTCH1 wild-type RB1 loss T-cell adult acute lymphocytic leukemia resistant Ribociclib Preclinical - Cell culture Actionable In a preclinical study, a T-cell acute lymphoblastic leukemia cell line harboring wild-type NOTCH1 and loss of RB1 demonstrated resistance to Kisqali (ribociclib) in culture, resulting in limited inhibition of cell growth (PMID: 28151717). 28151717
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
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia decreased response Ribociclib + Methotrexate Preclinical - Cell culture Actionable In a preclinical study, the addition of Kisqali (ribociclib) to Methotrexate resulted in an antagonistic effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and a NOTCH1 mutation in culture (PMID: 28151717). 28151717
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib + Dexamethasone Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Kisqali (ribociclib) and Adexone (dexamethasone) treatment in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and a NOTCH1 mutation resulted in decreased cell viability and reduced phosphorylation of Rb1 in culture, and a greater survival benefit in xenograft models when compared to Kisqali (ribociclib) alone (PMID: 28151717). 28151717
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib + Bortezomib Preclinical - Cell culture Actionable In a preclinical study, the combination of Kisqali (ribociclib) and Velcade (bortezomib) resulted in an additive effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and a NOTCH1 mutation in culture (PMID: 28151717). 28151717
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib + Everolimus Preclinical - Cell culture Actionable In a preclinical study, the combination of Kisqali (ribociclib) and Afinitor (everolimus) treatment in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and a NOTCH1 mutation resulted in decreased Rb1 phosphorylation and a greater inhibition of cell growth compared to either agent alone in culture (PMID: 28151717). 28151717
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib + Prednisolone Preclinical - Cell culture Actionable In a preclinical study, the combination of Kisqali (ribociclib) and Omnipred (prednisolone) resulted in a synergistic effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and a NOTCH1 mutation in culture (PMID: 28151717). 28151717
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia decreased response Ribociclib + Mercaptopurine Preclinical - Cell culture Actionable In a preclinical study, the addition of Kisqali (ribociclib) to Purixan (mercaptopurine) resulted in an antagonistic effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and a NOTCH1 mutation in culture (PMID: 28151717). 28151717
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib Preclinical - Cell culture Actionable In a preclinical study, a T-cell acute lymphoblastic leukemia cell line co-harboring wild-type RB1 and a NOTCH1 mutation demonstrated sensitivity to treatment with Kisqali (ribociclib) in culture, resulting in inhibition of cell growth (PMID: 28151717). 28151717
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia decreased response Ribociclib + Asparaginase Preclinical - Cell culture Actionable In a preclinical study, the addition of Kisqali (ribociclib) to Elspar (asparaginase) resulted in an antagonistic effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and a NOTCH1 mutation in culture (PMID: 28151717). 28151717
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Ribociclib + JQ1 Preclinical - Cell culture Actionable In a preclinical study, the combination of Kisqali (ribociclib) and JQ1 resulted in an additive effect in a T-cell acute lymphoblastic leukemia cell line harboring wild-type RB1 and a NOTCH1 mutation in culture (PMID: 28151717). 28151717
EML4-ALK NOTCH1 D1533A non-small cell lung carcinoma predicted - resistant Ceritinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK demonstrated resistance to treatment with Zykadia (ceritinib), and was subsequently found to have acquired NOTCH1 D1533A (PMID: 29636358). 29636358
NOTCH1 over exp Advanced Solid Tumor sensitive Brontictuzumab Phase I Actionable In a Phase I trial, Brontictuzumab (OMP-52M51) treatment resulted in stable disease in 43% (3/7) of advanced solid tumor patients with elevated levels of Notch1 intracellular domain (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C42). detail...
NOTCH1 V1599M osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 V1599M in culture (PMID: 25104330). 25104330
NOTCH1 E1567K osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 E1567K in culture (PMID: 25104330). 25104330
NOTCH1 A1707T osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 A1707T in culture (PMID: 25104330). 25104330
NOTCH1 A1707T Advanced Solid Tumor sensitive MRK-003 Preclinical Actionable In a preclinical study, transformed cells expressing NOTCH1 A1707T demonstrated sensitivity to MRK-003 in culture (PMID: 25104330). 25104330
NOTCH1 S2449fs 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 animal models of triple receptor negative breast cancer harboring NOTCH1 S2449fs (PMID: 25564152). 25564152
NOTCH1 R1683W osteosarcoma sensitive MRK-003 Preclinical Actionable In a preclinical study, MRK-003 inhibited Notch1 signaling in a luciferase reporter assay in osteosarcoma cell lines overexpressing NOTCH1 R1683W in culture (PMID: 25104330). 25104330
Clinical Trial Phase Therapies Title Recruitment Status