# NTRK1/2/3 gene fusion

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

## TL;DR

An NTRK fusion joins one of three TRK kinase genes to a partner and drives cancers from infant fibrosarcoma to salivary and thyroid tumours, rare in common cancers but near-universal in a few rare ones. Larotrectinib, entrectinib and repotrectinib are approved for it regardless of tumour type.

## Summary

NTRK1, NTRK2 and NTRK3 fusions (ETV6::NTRK3 in secretory carcinomas and infantile fibrosarcoma, LMNA::NTRK1 and TPM3::NTRK1 elsewhere) are best detected by RNA sequencing; DNA panels miss some NTRK2 and NTRK3 events because of long introns, and pan-TRK immunohistochemistry is a screen that needs molecular confirmation. Larotrectinib (2018) and entrectinib (2019) are labelled tumour-agnostically for solid tumours with an NTRK gene fusion without a known acquired resistance mutation, metastatic or where surgery would cause severe morbidity, with no satisfactory alternative or after progression; repotrectinib (2024) for NTRK fusion-positive solid tumours. FoundationOne CDx and Liquid CDx and TruSight Oncology Comprehensive are the listed companion diagnostics.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: NTRK fusion; NTRK gene fusion; TRK fusion; NTRK1 fusion; NTRK2 fusion; NTRK3 fusion; ETV6-NTRK3; ETV6::NTRK3; TRK fusion cancer; NTRK
- Tags: biomarker; fusion

## Notes

- Pancreatic ductal adenocarcinoma: NTRK fusions in about 0.4%, enriched in KRAS wild-type disease; the published pancreatic case 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% of tumours (cBioPortal), enriched in RAS and BRAF wild-type, mismatch repair deficient, right-sided disease. The threshold is the presence of a fusion on an RNA-based or fusion-capable DNA assay, and the approvals (larotrectinib, entrectinib) are tumour-agnostic.
- Gallbladder cancer: one LMNA::NTRK1 fusion patient among 233 (about 0.4%) in cBioPortal gbc_mskcc_2022; NTRK1 fusions were among the actionable findings (Giraldo 2022) and NTRK-driven biliary tumours retained the driver at progression (Cowzer 2026). RNA-based testing is needed because DNA panels miss some NTRK2 and NTRK3 events.
- Lung cancer: about 0.2% of adenocarcinomas by structural-variant calling (cBioPortal), covered by tumour-agnostic approvals rather than a lung indication. NTRK point mutations are common on exome panels and are passengers, so only a fusion assay gives an actionable result.

## Sources

- VITRAKVI prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c8ca614-58b2-4aa4-83d3-0387a8f782fd
- Rozlytrek prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7c71b0c-2549-4495-86b6-c2807fa54908

## Connected records

- biomarkers: [ALK fusion (ALK-positive)](https://onco.cc/biomarkers/alk-fusion/), [NRG1 gene fusion](https://onco.cc/biomarkers/nrg1-fusion/), [RET fusion and RET mutation](https://onco.cc/biomarkers/ret-fusion/), [ROS1 fusion (ROS1-positive)](https://onco.cc/biomarkers/ros1-fusion/)
- cancers: [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Metastatic cancer (cancer that has spread)](https://onco.cc/cancers/metastatic-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [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/)
- drugs: [Entrectinib](https://onco.cc/drugs/entrectinib/), [FoundationOne CDx / Liquid CDx](https://onco.cc/drugs/foundationone-cdx/), [Larotrectinib](https://onco.cc/drugs/larotrectinib/), [Repotrectinib](https://onco.cc/drugs/repotrectinib/), [TruSight Oncology Comprehensive](https://onco.cc/drugs/trusight-oncology-comprehensive/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/), [Tumour-agnostic (tissue-agnostic) approval](https://onco.cc/terms/tumour-agnostic/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- 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/)
- targets: [NTRK](https://onco.cc/targets/ntrk/)

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