{"entity":{"id":"ntrk","kind":"target","name":"NTRK","aka":[],"tldr":"Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it.","summary":"NTRK1, NTRK2 and NTRK3 encode the neurotrophin receptor kinases TrkA, TrkB and TrkC, and gene fusions lock them permanently on. Fusions are rare, under 1 percent of common adult cancers, yet near-universal in infantile fibrosarcoma (ETV6-NTRK3) and secretory carcinoma of breast and salivary gland, with 2 to 3 percent of thyroid cancers and rare colorectal cases enriched in MSI-high disease. Larotrectinib and entrectinib were the first kinase inhibitors approved on a tumour-agnostic basis (2018 to 2019), meaning any tumour with the fusion qualifies. Repotrectinib addresses acquired resistance mutations in the kinase domain. The open challenge is detection, because fusions this rare are only found when RNA-based or broad DNA panels are used routinely. The plain version: NTRK was the first target where a drug was approved for any cancer carrying it.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Trk_receptor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Trk_receptor"}],"tags":["driver","tumour-agnostic"],"related":["ntrk-fusion"],"cancers":["sarcoma","thyroid","colorectal","pancreatic","gallbladder","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["trk-950"],"companies":["lucence"],"institutions":[],"pathways":["ras-mapk","thyroid-cancer-signalling"],"terms":["gene-fusion","tumour-agnostic"],"trials":["nct06010342"],"people":[],"bottlenecks":[],"keyPapers":["paper-philip-kras-wild-type-pancreatic-ccr-2022","paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019","paper-giraldo-gallbladder-msk-impact-ccr-2022","paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026"],"journals":[],"dependsOn":[],"notes":["Pancreatic ductal adenocarcinoma: NTRK fusions in about 0.4% (ETV6-NTRK3 and CTRC-NTRK1 the commonest; cBioPortal pdac_msk_2024), enriched in KRAS wild-type disease. A CTRC-NTRK1 fusion cancer responded to larotrectinib for six months under the tumour-agnostic approval before acquiring resistance (O'Reilly and Hechtman 2019).","Colorectal cancer: NTRK1 and NTRK3 fusions in about 0.2 to 0.3% (LMNA-NTRK1 and ETV6-NTRK3 the commonest; cBioPortal), concentrated in RAS and BRAF wild-type, mismatch repair deficient, right-sided tumours. The approvals, larotrectinib and entrectinib, are tumour-agnostic; the practical rule is to run a fusion assay when a right-sided MSI-high tumour reads wild-type on a DNA panel.","Gallbladder cancer: one LMNA::NTRK1 fusion patient among 233 in cBioPortal gbc_mskcc_2022 (about 0.4%); NTRK-driven biliary tumours retained the driver at progression (Cowzer 2026).","Lung cancer: fusions in about 0.2% of adenocarcinomas (cBioPortal), the rarest of the licensed targets and covered by a tumour-agnostic approval rather than a lung indication. NTRK point mutations read 2 to 8% on exome panels and are passengers."],"symbol":"NTRK1/2/3","role":[],"sources":[],"specificity":"tumour-specific","distribution":"many-types","tumourAgnostic":true,"specificityNote":"Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (NTRK1/2/3 gene fusion) absent from normal cells. HPA NTRK1: RNA tissue enhanced (adrenal gland 7 nTPM); blood lineage lineage enriched (granulocytes 95 nTPM); no normal tissue stained high. HPA NTRK2: RNA tissue enhanced (brain 233 nTPM, thyroid gland 118 nTPM); high antibody staining in 2 normal tissues. HPA NTRK3: RNA group enriched (blood vessel 67 nTPM, brain 28 nTPM); high antibody staining in 1 normal tissue; highest cancer staining ovarian cancer (1 of 11 high). Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Sarcomas (soft tissue, bone, GIST), Thyroid cancer, Colorectal cancer, Biliary tract cancer (all types)); approvals of single-target medicines aimed at it also list Salivary gland cancers, Lung cancer (all types), Pancreatic ductal adenocarcinoma, not counted; Open Targets associates it with 3 specific cancer types at or above 0.5 (non-small cell lung carcinoma, colorectal cancer, familial medullary thyroid carcinoma). Tissue-agnostic: NTRK1/2/3 gene fusion threshold \"NTRK gene fusion without a known acquired resistance mutation\" for Larotrectinib is tissue-agnostic; NTRK1/2/3 gene fusion threshold \"NTRK gene fusion in tumour or plasma\" for Entrectinib is tissue-agnostic; Entrectinib JP 2019: \"NTRK fusion solid tumours\". (Rule 3 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"NTRK1/2/3 gene fusion label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c8ca614-58b2-4aa4-83d3-0387a8f782fd","note":"NTRK gene fusion without a known acquired resistance mutation"},{"label":"Human Protein Atlas NTRK1 tissue","url":"https://www.proteinatlas.org/ENSG00000198400-NTRK1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas NTRK2 tissue","url":"https://www.proteinatlas.org/ENSG00000148053-NTRK2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas NTRK3 tissue","url":"https://www.proteinatlas.org/ENSG00000140538-NTRK3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"NTRK1/2/3 gene fusion label","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7c71b0c-2549-4495-86b6-c2807fa54908","note":"NTRK gene fusion in tumour or plasma"},{"label":"Open Targets ENSG00000198400 associations","url":"https://platform.opentargets.org/target/ENSG00000198400/associations","note":"cancer associations at or above 0.5 (CC0)"},{"label":"Open Targets ENSG00000148053 associations","url":"https://platform.opentargets.org/target/ENSG00000148053/associations","note":"cancer associations at or above 0.5 (CC0)"}],"biology":"NTRK1/2/3 encode the neurotrophin receptor kinases TrkA, TrkB and TrkC.","whereFound":["Infantile fibrosarcoma","Secretory breast/salivary carcinoma","Thyroid, colorectal, lung (rare)","Pancreatic ductal adenocarcinoma: gene fusion (etv6-ntrk3, ctrc-ntrk1) 0.4%","Colorectal cancer: gene fusion (lmna-ntrk1, etv6-ntrk3) 0.2-0.3%","Gallbladder cancer: gene fusion 0.4%","Non-small-cell lung cancer: ntrk1, ntrk2 or ntrk3 rearrangement about 0.2%"],"targetClass":"kinase","prevalence":[{"cancerId":"sarcoma","pct":">90","measure":"Infantile fibrosarcoma (ETV6-NTRK3)","source":"https://en.wikipedia.org/wiki/Trk_receptor","note":"<1% in adult common cancers"},{"cancerId":"thyroid","pct":"2-3","measure":"Fusion","source":"https://en.wikipedia.org/wiki/Trk_receptor"},{"cancerId":"colorectal","pct":"<1","measure":"Fusion","source":"https://en.wikipedia.org/wiki/Trk_receptor","note":"Enriched in MSI-high"},{"cancerId":"pancreatic","pct":"0.4","measure":"Gene fusion (ETV6-NTRK3, CTRC-NTRK1)","source":"https://www.cbioportal.org/study/summary?id=pdac_msk_2024","note":"cBioPortal structural variants: 9 of 2,336, 0.4% (ETV6-NTRK3 3, CTRC-NTRK1 2, EML4-NTRK1, COP1-NTRK1), in pdac_msk_2024; 2 of 184 (CEL-NTRK1, EML4-NTRK3) in paad_tcga_pan_can_atlas_2018; NTRK amplification 1.8% of 266 KRAS wild-type tumours (Philip 2022). A CTRC-NTRK1 fusion cancer responded to larotrectinib for 6 months before resistance (O'Reilly and Hechtman 2019)."},{"cancerId":"colorectal","pct":"0.2-0.3","measure":"Gene fusion (LMNA-NTRK1, ETV6-NTRK3)","source":"https://www.cbioportal.org/study/summary?id=crc_msk_2026","note":"cBioPortal structural variants: NTRK1 in 13 of 7,237, 0.18% (LMNA-NTRK1 6), and NTRK3 in 5, in crc_msk_2026; NTRK1 in 5 of 1,134 (LMNA-NTRK1 4) in crc_msk_2017; NTRK3 in 3 of 594 (ETV6-NTRK3 2) in coadread_tcga_pan_can_atlas_2018; NTRK1 in 4 of 1,516 in crc_eo_2020."},{"cancerId":"gallbladder","pct":"0.4","measure":"Gene fusion","source":"https://www.cbioportal.org/study/summary?id=gbc_mskcc_2022","note":"One LMNA::NTRK1 fusion patient (four samples) among 233 patients in cBioPortal gbc_mskcc_2022, about 0.4%; NTRK1 fusions named among the actionable alterations (Giraldo 2022); NTRK-driven biliary tumours retained the driver at progression (Cowzer 2026)."},{"cancerId":"nsclc","pct":0.2,"measure":"NTRK1, NTRK2 or NTRK3 rearrangement","source":"https://www.cbioportal.org/study/summary?id=luad_mskcc_2023_met_organotropism","note":"cBioPortal structural variants: 5 of 2,422, 0.2%, in luad_mskcc_2023_met_organotropism; 1 of 2,621, 0.04%, in nsclc_ctdx_msk_2022; 1 of 510 in luad_tcga_pan_can_atlas_2018."}]},"route":"/targets/ntrk/","neighbours":{"biomarker":[{"id":"ntrk-fusion","kind":"biomarker","name":"NTRK1/2/3 gene fusion","route":"/biomarkers/ntrk-fusion/"}],"cancer":[{"id":"ampullary","kind":"cancer","name":"Ampullary cancer (ampulla of Vater)","route":"/cancers/ampullary/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"cancer-of-unknown-primary","kind":"cancer","name":"Cancer of unknown primary (CUP)","route":"/cancers/cancer-of-unknown-primary/"},{"id":"cup-unfavourable","kind":"cancer","name":"Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma)","route":"/cancers/cup-unfavourable/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"gist","kind":"cancer","name":"Gastrointestinal stromal tumour (GIST)","route":"/cancers/gist/"},{"id":"inflammatory-myofibroblastic-tumour","kind":"cancer","name":"Inflammatory myofibroblastic tumour (IMT)","route":"/cancers/inflammatory-myofibroblastic-tumour/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"ntrk-fusion-nsclc","kind":"cancer","name":"NTRK fusion-positive non-small-cell lung cancer","route":"/cancers/ntrk-fusion-nsclc/"},{"id":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline glioma)","route":"/cancers/paediatric-high-grade-glioma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"ros1-positive-nsclc","kind":"cancer","name":"ROS1-positive non-small-cell lung cancer","route":"/cancers/ros1-positive-nsclc/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"},{"id":"uterine-sarcoma","kind":"cancer","name":"Uterine sarcoma","route":"/cancers/uterine-sarcoma/"}],"drug":[{"id":"entrectinib","kind":"drug","name":"Entrectinib","route":"/drugs/entrectinib/"},{"id":"larotrectinib","kind":"drug","name":"Larotrectinib","route":"/drugs/larotrectinib/"},{"id":"repotrectinib","kind":"drug","name":"Repotrectinib","route":"/drugs/repotrectinib/"},{"id":"trk-950","kind":"drug","name":"TRK-950","route":"/drugs/trk-950/"},{"id":"trusight-oncology-comprehensive","kind":"drug","name":"TruSight Oncology Comprehensive","route":"/drugs/trusight-oncology-comprehensive/"}],"company":[{"id":"lucence","kind":"company","name":"Lucence","route":"/companies/lucence/"}],"pathway":[{"id":"cancer-neuroscience","kind":"pathway","name":"Cancer neuroscience (nerve-tumour signalling)","route":"/pathways/cancer-neuroscience/"},{"id":"pancreatic-cancer-signalling","kind":"pathway","name":"Pancreatic cancer (KEGG map)","route":"/pathways/pancreatic-cancer-signalling/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"},{"id":"thyroid-cancer-signalling","kind":"pathway","name":"Thyroid cancer (KEGG map)","route":"/pathways/thyroid-cancer-signalling/"}],"term":[{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"trial":[{"id":"nct06010342","kind":"trial","name":"A Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients","route":"/trials/nct06010342/"},{"id":"navigate","kind":"trial","name":"NAVIGATE","route":"/trials/navigate/"}],"paper":[{"id":"paper-giraldo-gallbladder-msk-impact-ccr-2022","kind":"paper","name":"Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention","route":"/key-papers/paper-giraldo-gallbladder-msk-impact-ccr-2022/"},{"id":"paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026","kind":"paper","name":"Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer","route":"/key-papers/paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026/"},{"id":"paper-philip-kras-wild-type-pancreatic-ccr-2022","kind":"paper","name":"Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma","route":"/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/"},{"id":"paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019","kind":"paper","name":"Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion","route":"/key-papers/paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"person":[{"id":"alexander-drilon","kind":"person","name":"Alexander Drilon","route":"/people/alexander-drilon/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"}],"idea":[{"id":"idea-tr1-tumour-agnostic-approval-standard","kind":"idea","name":"A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling","route":"/ideas/idea-tr1-tumour-agnostic-approval-standard/"},{"id":"idea-reg-tumour-agnostic-reliance","kind":"idea","name":"Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review","route":"/ideas/idea-reg-tumour-agnostic-reliance/"},{"id":"idea-moon-reciprocal-tumour-agnostic-approvals","kind":"idea","name":"Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators","route":"/ideas/idea-moon-reciprocal-tumour-agnostic-approvals/"}],"institution":[{"id":"colorado-cancer-center","kind":"institution","name":"University of Colorado Cancer Center","route":"/institutions/colorado-cancer-center/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}