# NTRK

Source: https://onco.cc/targets/ntrk/  
OnCo record `ntrk` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: driver; tumour-agnostic
- Symbol: NTRK1/2/3
- Class: kinase
- Biology: NTRK1/2/3 encode the neurotrophin receptor kinases TrkA, TrkB and TrkC.
- Where found: 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%

## 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Trk_receptor
- Wikipedia: https://en.wikipedia.org/wiki/Trk_receptor

## Connected records

- biomarkers: [NTRK1/2/3 gene fusion](https://onco.cc/biomarkers/ntrk-fusion/)
- cancers: [Ampullary cancer (ampulla of Vater)](https://onco.cc/cancers/ampullary/), [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Cancer of unknown primary (CUP)](https://onco.cc/cancers/cancer-of-unknown-primary/), [Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma)](https://onco.cc/cancers/cup-unfavourable/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Gastrointestinal stromal tumour (GIST)](https://onco.cc/cancers/gist/), [Inflammatory myofibroblastic tumour (IMT)](https://onco.cc/cancers/inflammatory-myofibroblastic-tumour/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [NTRK fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ntrk-fusion-nsclc/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [ROS1-positive non-small-cell lung cancer](https://onco.cc/cancers/ros1-positive-nsclc/), [Salivary gland cancers](https://onco.cc/cancers/salivary-gland/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Thyroid cancer](https://onco.cc/cancers/thyroid/), [Uterine sarcoma](https://onco.cc/cancers/uterine-sarcoma/)
- drugs: [Entrectinib](https://onco.cc/drugs/entrectinib/), [Larotrectinib](https://onco.cc/drugs/larotrectinib/), [Repotrectinib](https://onco.cc/drugs/repotrectinib/), [TRK-950](https://onco.cc/drugs/trk-950/), [TruSight Oncology Comprehensive](https://onco.cc/drugs/trusight-oncology-comprehensive/)
- companies: [Lucence](https://onco.cc/companies/lucence/)
- pathways: [Cancer neuroscience (nerve-tumour signalling)](https://onco.cc/pathways/cancer-neuroscience/), [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/), [Thyroid cancer (KEGG map)](https://onco.cc/pathways/thyroid-cancer-signalling/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/), [Tumour-agnostic (tissue-agnostic) approval](https://onco.cc/terms/tumour-agnostic/)
- trials: [A Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients](https://onco.cc/trials/nct06010342/), [NAVIGATE](https://onco.cc/trials/navigate/)
- key papers: [Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention](https://onco.cc/key-papers/paper-giraldo-gallbladder-msk-impact-ccr-2022/), [Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer](https://onco.cc/key-papers/paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026/), [Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/), [Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion](https://onco.cc/key-papers/paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- people: [Alexander Drilon](https://onco.cc/people/alexander-drilon/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)
- ideas: [A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling](https://onco.cc/ideas/idea-tr1-tumour-agnostic-approval-standard/), [Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review](https://onco.cc/ideas/idea-reg-tumour-agnostic-reliance/), [Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators](https://onco.cc/ideas/idea-moon-reciprocal-tumour-agnostic-approvals/)
- institutions: [University of Colorado Cancer Center](https://onco.cc/institutions/colorado-cancer-center/)
- roadmaps: [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

---
JSON: https://onco.cc/api/v1/entities/ntrk.json