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Gene ETV6 NTRK3
Variant ETV6 - NTRK3
Impact List fusion
Protein Effect gain of function
Gene Variant Descriptions ETV6-NTRK3 results from the fusion of ETV6 and NTRK3, which leads to ligand-independent dimerization and activation of the fusion protein, transformation in cultured cells and tumor formation in animal models (PMID: 10702799). ETV6-NTRK3 fusions are associated with secretory breast carcinoma (PMID: 17425505).
Associated Drug Resistance

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No Variant Reference Transcript is Available.
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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
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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ETV6 - NTRK3 breast cancer sensitive BMS-754807 Preclinical - Cell line xenograft Actionable In a preclinical study, BMS-754807 inhibited tumor growth in cell line xenograft models of breast cancer cells overexpressing ETV6-NTRK3 (PMID: 21148487). 21148487
ETV6 - NTRK3 salivary gland cancer predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a brief stable disease in a patient with mammary analogue secretory carcinoma of the salivary gland harboring ETV6-NTRK3, before disease progression at 18 weeks (PMID: 26884591). 26884591
ETV6 - NTRK3 Advanced Solid Tumor sensitive Altiratinib Preclinical Actionable In a preclinical study, transformed cells expressing ETV6-NTRK3 demonstrated sensitivity to Altiratinib (DCC-2701) in culture, resulting in inhibition of Ntrk3 phosphorylation and decreased cell proliferation (AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 790). detail...
ETV6 - NTRK3 acute myeloid leukemia sensitive CH7057288 Preclinical - Cell line xenograft Actionable In a preclinical study, CH7057288 inhibited NTRK phosphorylation and downstream signaling and reduced growth of acute myeloid leukemia cells harboring ETV6-NTRK3 in culture, and induced tumor regression in xenograft models (PMID: 30242093). 30242093
ETV6 - NTRK3 acute myeloid leukemia sensitive Larotrectinib Preclinical Actionable In a preclinical study, Vitrakvi (larotrectinib) inhibited cell growth and downstream signaling in acute myeloid leukemia cells harboring ETV6-NTRK3 in culture and xenografts (PMID: 26216294). 26216294
ETV6 - NTRK3 gastrointestinal stromal tumor predicted - sensitive Larotrectinib Case Reports/Case Series Actionable In a Phase I trial, Vitrakvi (larotrectinib) treatment resulted in complete response in 1 and partial response in 2 patients with gastrointestinal stromal tumor harboring ETV6-NTRK3 fusions (PMID: 29466156, Annals of Oncology, Volume 29, Issue suppl_5; NCT02122913, NCT02637687, and NCT02576431). 29466156 detail...
ETV6 - NTRK3 Advanced Solid Tumor sensitive BMS-536924 Preclinical Actionable In a preclinical study, transformed human cells expressing ETV6-NTRK3 were sensitive to BMS-536924, demonstrating a reduction in both cell survival and transformation activity in culture (PMID: 21804605). 21804605
ETV6 - NTRK3 congenital fibrosarcoma sensitive Larotrectinib Phase I Actionable In a Phase I clinical trial, treatment with Vitrakvi (larotrectinib) resulted in a partial response in a pediatric patient with infantile fibrosarcoma harboring ETV6-NTRK3 (PMID: 27093299). 27093299
ETV6 - NTRK3 congenital fibrosarcoma sensitive Larotrectinib Phase Ib/II Actionable In a Phase I/II trial, Vitrakvi (larotrectinib) treatment resulted in complete response in 33.3% (2/6) and partial response in 66.7% (4/6) of pediatric patients with congenital fibrosarcoma harboring ETV6-NTRK3 fusions (PMID: 29606586; NCT02637687). 29606586
ETV6 - NTRK3 congenital fibrosarcoma sensitive Larotrectinib Case Reports/Case Series Actionable In a clinical case study, a patient with congenital fibrosarcoma harboring ETV6-NTRK3 demonstrated tumor regression by 90% when treated with Vitrakvi (larotrectinib) (PMID: 28578312). 28578312
ETV6 - NTRK3 Advanced Solid Tumor sensitive Larotrectinib Phase II Actionable In a combined analysis of three trials, Vitrakvi (larotrectinib) treatment resulted in complete response in 21.4% (6/28) and partial response in 67.9% (19/28) of patients with advanced solid tumors harboring an ETV6-NTRK3 fusion (PMID: 29466156; NCT02122913, NCT02637687, NCT02576431). 29466156
ETV6 - NTRK3 Advanced Solid Tumor sensitive Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited proliferation of transformed cells expressing ETV6-NTRK3 in culture (PMID: 30093503). 30093503
ETV6 - NTRK3 Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ETV6-NTRK3 were sensitive to Rozlytrek (entrectinib), resulting in inhibition of cell proliferation in culture (PMID: 26939704). 26939704
ETV6 - NTRK3 Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ETV6-NTRK3 were sensitive to Rozlytrek (entrectinib) as demonstrated by reduced proliferation relative to cells expressing an empty vector in culture (PMID: 26884591). 26884591
ETV6 - NTRK3 melanoma sensitive DS-6051a Preclinical - Cell culture Actionable In a preclinical study, DS-6051a inhibited MAPK, PI3K, and PLCgamma-1 signaling in transformed melanocytes expressing ETV6-NTRK3 in culture (PMID: 27477320). 27477320
ETV6 - NTRK3 small intestine neuroendocrine neoplasm predicted - sensitive Entrectinib Case Reports/Case Series Actionable In a clinical study, Rozlytrek (entrectinib) treatment resulted in rapid response and tumor necrosis in a patient with a small intestine neuroendocrine tumor harboring a ETV6-NTRK3 fusion (PMID: 29118225; NCT02568267). 29118225
ETV6 - NTRK3 congenital fibrosarcoma not applicable N/A Guideline Diagnostic ETV6-NTRK3 fusions aid the diagnosis of congenital fibrosarcoma (NCCN.org). detail...
ETV6 - NTRK3 pancreatic cancer predicted - sensitive PLX7486 Case Reports/Case Series Actionable In a clinical case study, a patient with pancreatic cancer harboring ETV6-NTRK3 demonstrated a prolonged response when treated with PLX7486 (PMID: 31406350). 31406350
ETV6 - NTRK3 acute myeloid leukemia sensitive Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) inhibited ETV6-NTRK3 activity, reduced cell growth in a human acute myeloid leukemia cell line harboring ETV6-NTRK3, and had anti-tumor activity in xenograft models (PMID: 23811600). 23811600
ETV6 - NTRK3 Advanced Solid Tumor sensitive Lestaurtinib Preclinical Actionable In a preclinical study, transformed cells expressing the fusion, ETV6-NTRK3, were treated with Lestaurtinib (CEP-701), which resulted in inhibition of ETV6-NTRK3 autophosphorylation and restoration of Tgf-b1 signaling (PMID: 16258068). 16258068
ETV6 - NTRK3 head and neck squamous cell carcinoma sensitive Merestinib Preclinical - Pdx Actionable In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring ETV6-NTRK3 was sensitive to treatment with Merestinib (LY2801653) compared to vehicle, demonstrating decreased tumor growth (PMID: 29568395). 29568395
ETV6 - NTRK3 fibrosarcoma predicted - sensitive Entrectinib Phase I Actionable In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in an objective response in a pediatric patient with infantile fibrosarcoma harboring ETV6-NTRK3 fusion (J Clin Oncol 36, 2018 (suppl; abstr 10536); NCT02650401). detail...
ETV6 - NTRK3 cancer sensitive Midostaurin Preclinical Actionable In a preclinical study, the broad spectrum kinase inhibitor midostaurin inhibited growth of cells dependent on the fusion protein ETV6-NTRK3, reducing ETV6-NTRK3 kinase activity and downstream signaling and inducing apoptosis (PMID: 23131561). 23131561
ETV6 - NTRK3 Advanced Solid Tumor sensitive DS6051b Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ETV6-NTRK3 were sensitive to treatment with DS6051b in culture, demonstrating cell growth inhibition (PMID: 31399568). 31399568
ETV6 - NTRK3 salivary gland cancer predicted - sensitive Entrectinib Case Reports/Case Series Actionable In a clinical case study, treatment with Rozlytrek (entrectinib) obtained through a Phase I trial resulted in a durable partial response in a patient with mammary analogue secretory carcinoma of the salivary gland harboring ETV6-NTRK3 (PMID: 26884591; NCT02097810). 26884591
ETV6 - NTRK3 B-lymphoblastic leukemia/lymphoma with BCR-ABL1 predicted - sensitive Larotrectinib Case Reports/Case Series Actionable In a clinical case study, Vitrakvi (larotrectinib) treatment resulted in significant suppression of leukemic cells and clinical benefit in a patient with relapsed Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia associated with an expansion of a subclone harboring ETV6-NTRK3 fusion (PMID: 31905241). 31905241
ETV6 - NTRK3 MAP2K1 P124S pancreatic cancer predicted - resistant LOXO-195 Case Reports/Case Series Actionable In a clinical case study, a secondary resistance mutation, MAP2K1 P124S, was identified via cell-free DNA testing after a patient with pancreatic cancer harboring ETV6-NTRK3 progressed on LOXO-195 treatment (PMID: 31406350). 31406350
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ETV6 mutant myelodysplastic syndrome not applicable N/A Guideline Prognostic ETV6 mutations are associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
ETV6 mutant myelodysplastic syndrome not applicable N/A Clinical Study Prognostic In multiple clinical studies, ETV6 mutations were associated with a shorter overall survival in patients with myelodysplastic syndrome (PMID: 21714648, PMID: 21877899, PMID: 26769228). 21877899 26769228 21714648