Molecular Profile Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Profile Name NOTCH1 mutant
Gene Variant Detail

NOTCH1 mutant (unknown)

Relevant Treatment Approaches

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 prostate cancer predicted - sensitive Docetaxel + PF-03084014 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 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 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 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 S1004L adenoid cystic carcinoma no benefit Brontictuzumab Preclinical - Pdx Actionable In a preclinical study, Brontictuzumab (OMP-52M51) did not inhibit tumor growth in a patient-derived xenograft model of adenoid cystic carcinoma harboring NOTCH1 S1004L (PMID: 27870570). 27870570
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 + 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 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 C344fs head and neck squamous cell carcinoma predicted - sensitive GSK2126458 Preclinical - Cell culture Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line harboring NOTCH1 C344fs demonstrated apoptotic activity and reduced colony growth when treated with GSK2126458 in culture (PMID: 30770351). 30770351
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 E1679* head and neck squamous cell carcinoma predicted - sensitive GSK2126458 Preclinical - Cell line xenograft Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line harboring NOTCH1 E1679* demonstrated apoptotic activity and reduced colony growth in culture and tumor regression in cell line xenograft models when treated with GSK2126458 (PMID: 30770351). 30770351
NOTCH1 Q1957* head and neck squamous cell carcinoma predicted - sensitive GSK2126458 Preclinical - Cell culture Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line harboring NOTCH1 Q1957* demonstrated apoptotic activity and reduced colony growth when treated with GSK2126458 in culture (PMID: 30770351). 30770351
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 G192* head and neck squamous cell carcinoma predicted - sensitive GSK2126458 Preclinical - Cell culture Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line harboring NOTCH1 G192* demonstrated apoptotic activity and reduced colony growth when treated with GSK2126458 in culture (PMID: 30770351). 30770351
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 E694* head and neck squamous cell carcinoma predicted - sensitive GSK2126458 Preclinical - Cell culture Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line harboring NOTCH1 E694* demonstrated apoptotic activity and reduced colony growth when treated with GSK2126458 in culture (PMID: 30770351). 30770351
EML4 - ALK NOTCH1 D1533A lung non-small cell carcinoma predicted - resistant Ceritinib Case Reports/Case Series 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 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 V489fs head and neck squamous cell carcinoma predicted - sensitive GSK2126458 Preclinical - Cell culture Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line harboring NOTCH1 V489fs demonstrated apoptotic activity and reduced colony growth when treated with GSK2126458 in culture (PMID: 30770351). 30770351
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
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 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 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 RB1 wild-type T-cell adult acute lymphocytic leukemia decreased response Methotrexate + Ribociclib 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 sensitive JQ1 + Ribociclib 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 Bortezomib + Ribociclib 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 conflicting Dexamethasone + Ribociclib 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 Mercaptopurine + Ribociclib 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 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 sensitive Everolimus + Ribociclib 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 decreased response Asparaginase + Ribociclib 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 Prednisolone + Ribociclib 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 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
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 mut RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Everolimus + Ribociclib 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 Prednisolone + Ribociclib 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 Mercaptopurine + Ribociclib 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 JQ1 + Ribociclib 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
NOTCH1 mut RB1 wild-type T-cell adult acute lymphocytic leukemia sensitive Bortezomib + Ribociclib 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 decreased response Asparaginase + Ribociclib 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 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 Methotrexate + Ribociclib 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 Dexamethasone + Ribociclib 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 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 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 L1600Q NOTCH1 S2467fs adenoid cystic carcinoma predicted - sensitive Brontictuzumab Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic adenoid cystic carcinoma harboring co-occurring NOTCH1 L1600Q and S2467fs achieved a partial response after 2 doses of Brontictuzumab (OMP-52M51), however, his disease progressed shortly after treatment discontinuation (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 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
NOTCH1 H2018fs head and neck squamous cell carcinoma predicted - sensitive GSK2126458 Preclinical - Cell culture Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line harboring NOTCH1 H2018fs demonstrated apoptotic activity and reduced colony growth when treated with GSK2126458 in culture (PMID: 30770351). 30770351
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
EML4 - ALK NOTCH1 D1538A lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series 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
NOTCH1 C478F head and neck squamous cell carcinoma predicted - sensitive GSK2126458 Preclinical - Cell line xenograft Actionable In a preclinical study, a head and neck squamous cell carcinoma cell line harboring NOTCH1 C478F demonstrated apoptotic activity and reduced colony growth in culture and tumor regression in cell line xenograft models when treated with GSK2126458 (PMID: 30770351). 30770351
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 C478F head and neck squamous cell carcinoma predicted - sensitive PQR309 Preclinical - Cell line xenograft Actionable In a preclinical study, head and neck squamous cell carcinoma xenograft models harboring NOTCH1 C478F demonstrated reduced tumor size when treated with PQR309 (bimiralisib) (PMID: 30770351). 30770351
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
ROS1 fusion ERBB2 amp NOTCH1 amp SRC amp STK11 amp lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series 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 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 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 I1680N adenoid cystic carcinoma predicted - sensitive Brontictuzumab Preclinical - Pdx Actionable In a preclinical study, Brontictuzumab (OMP-52M51) inhibited tumor growth in a patient-derived xenograft model of adenoid cystic carcinoma harboring NOTCH1 I1680N (PMID: 27870570). 27870570
Clinical Trial Phase Therapies Title Recruitment Status
NCT02869633 Phase II Ibrutinib Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant Active, not recruiting
NCT03204188 Phase II Fludarabine + Ibrutinib + Pembrolizumab Ibrutinib, Fludarabine, and Pembrolizumab in High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Recruiting
NCT02784795 Phase I Cisplatin + Gemcitabine + LY3039478 Carboplatin + Gemcitabine + LY3039478 LY3023414 + LY3039478 Abemaciclib + LY3039478 LY3039478 + Taladegib LY3039478 LY3023414 A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors Completed