Loading
Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it.
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.
In plain words · Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it.
Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it.
NTRK1/2/3 encode the neurotrophin receptor kinases TrkA, TrkB and TrkC.
5 products aim at NTRK: antibodies, small molecules and other agents. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
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.)
Sources: NTRK1/2/3 gene fusion label threshold; Human Protein Atlas NTRK1 tissue; Human Protein Atlas NTRK2 tissue; Human Protein Atlas NTRK3 tissue; NTRK1/2/3 gene fusion label; Open Targets ENSG00000198400 associations; Open Targets ENSG00000148053 associations
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
NTRK1/2/3 encode the neurotrophin receptor kinases TrkA, TrkB and TrkC.
RNA: tissue enhanced (adrenal gland 7 nTPM), detected in some normal tissues. Blood: lineage enriched (granulocytes 95 nTPM).
No normal tissue stained high; medium in Cerebral cortex, Testis.
No cancer sample stained medium or high.
HPA NTRK1 tissue · HPA NTRK1 pathology · HPA protein class: FDA approved drug targets
RNA: tissue enhanced (brain 233 nTPM, thyroid gland 118 nTPM), detected in many normal tissues.
Medium: Caudate.
RNA cancer enhanced: Glioblastoma Multiforme 136 pTPM, Thyroid Carcinoma 105 pTPM.
No cancer sample stained medium or high.
HPA NTRK2 tissue · HPA NTRK2 pathology · HPA protein class: FDA approved drug targets
RNA: group enriched (blood vessel 67 nTPM, brain 28 nTPM), detected in many normal tissues.
Medium: Adrenal gland, Bone marrow, Bronchus, Caudate, Cerebellum, Cervix, Colon, Heart muscle.
RNA group enriched: Glioblastoma Multiforme 23 pTPM, Testicular Germ Cell Tumor 10 pTPM.
Medium only: cervical cancer, colorectal cancer, liver cancer, lung cancer.
HPA NTRK3 tissue · HPA NTRK3 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Sarcomas | >90% | Infantile fibrosarcoma (ETV6-NTRK3) | <1% in adult common cancers | Wikipedia |
| Thyroid cancer | 2-3% | Fusion | Wikipedia | |
| Colorectal cancer | <1% | Fusion | Enriched in MSI-high | Wikipedia |
| Pancreatic ductal adenocarcinoma | 0.4% | Gene fusion (ETV6-NTRK3, CTRC-NTRK1) | 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). | cBioPortal (TCGA) |
| Gallbladder cancer | 0.4% | Gene fusion | 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). | cBioPortal (TCGA) |
| Colorectal cancer | 0.2-0.3% | Gene fusion (LMNA-NTRK1, ETV6-NTRK3) | 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. | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 0.2% | NTRK1, NTRK2 or NTRK3 rearrangement | 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. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.
The first drug approved for a gene fusion regardless of where the cancer started; it works in about 75% of NTRK-fusion cancers, from infant fibrosarcoma to salivary and thyroid cancers.
A ROS1 and NTRK pill that also works after other ROS1 drugs fail, with dizziness as its signature side effect.
TRK-950 is an experimental investigational agent whose form is not stated in the registry from Toray Industries in phase 2 trials for gastric & gastro-oesophageal junction cancer and melanoma, aimed at NTRK.
A large gene panel hospitals can run themselves, approved by the FDA in 2024 as a companion diagnostic for the tumour-agnostic drug larotrectinib.
For gallbladder cancer the points that matter are that HER2 can disappear under HER2-directed pressure, that SMAD4 co-mutation predicts a worse response, and that sequencing at progression, not just at diagnosis, may be needed to guide the next line.
The reference Western cohort for gallbladder cancer frequencies, deposited on cBioPortal as gbc_mskcc_2022, where the per-gene sample counts on OnCo were read. It supports panel testing at diagnosis: one patient in three has a targetable finding.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
NTRK fusions are under 0.5% of pancreatic cancers but carry a tumour-agnostic approval; this case is the published proof that the label applies here.
Query for this target: (TITLE:"NTRK" OR ABSTRACT:"NTRK" OR TITLE:"NTRK1" OR ABSTRACT:"NTRK1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NTRK, not a curated reading list.
Shares Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review, Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling, Lucence and the tag driver.
Shares Alexander Drilon, University of Colorado Cancer Center, Repotrectinib, Inflammatory myofibroblastic tumour (IMT) and the tag driver.
Shares Lucence, Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer, Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Thyroid cancer (KEGG map) and the tag driver.
Shares Lucence, University of Colorado Cancer Center, Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma, Inflammatory myofibroblastic tumour (IMT) and the tag driver.
Shares Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review, Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling, Thyroid cancer (KEGG map) and the tag driver.
Shares Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma, KRAS wild-type pancreatic ductal adenocarcinoma, Gene fusion and the tag driver.
Shares Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer, Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma, Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma) and the tag driver.
Shares Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Pancreatic cancer (KEGG map), Receptor tyrosine kinase activation, Gallbladder cancer and the tag driver.