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Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it. This dossier gathers the 5 products (4 approved), 21 trials, 1 pathway and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
NTRK1/2/3 encode the neurotrophin receptor kinases TrkA, TrkB and TrkC.
| 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.
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| G595R (solvent front) 595 | Resistance | not sourced | The main acquired escape from larotrectinib and entrectinib; repotrectinib covers it. | Drilon et al., Cancer Discov 2017 | ||
| G667C (xDFG) and F589L (gatekeeper) 667 | Resistance | not sourced | Further on-target escapes with partial coverage by next-generation TRK inhibitors. | Drilon et al., Cancer Discov 2017 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: COSMIC: NTRK1.
| Modality | Approved | Phase 2 |
|---|---|---|
| Small molecule 2 | - | |
| Antibody 1 | - | |
| Small-molecule TRK/ROS1/ALK TKI 1 | - | |
| Test or device 1 | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | A Phase I-III, Multicenter Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Patients Selected According to Biomarker Status, With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer | - | ||
| 3 | Active | Randomized, Open-label, Multicenter, Phase 3 Trial of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3) | - | ||
| 3 | Active | Randomized, Open Label, Multicenter, Phase III Study of Entrectinib Versus Crizotinib in Patients With Locally-Advanced or Metastatic Non-Small Cell Lung Cancer Harboring ROS1 Gene Rearrangements With and Without Central Nervous System Metastases | - | ||
NCI-COG Pediatric MATCH (APEC1621) NCT03155620 | platform | Active | Relapsed or refractory solid tumours, non-Hodgkin lymphomas and histiocytic disorders, age 1-21: tumour sequencing then assignment to one of a dozen single-agent targeted-therapy phase 2 arms | Actionable alteration in 31.5% of the first 1,000 tumours; 28.4% assigned and 13.1% enrolled on a treatment arm. | |
NCI-MATCH (EAY131) NCT02465060 | platform | Active | Advanced solid tumours, lymphomas and myeloma that have progressed on standard treatment: central tumour sequencing assigns patients to one of nearly 40 single-agent or doublet targeted-therapy arms by molecular alteration regardless of cancer type | 5,954 patients enrolled; 17.8 percent assigned to an arm. Dabrafenib plus trametinib in BRAF V600 tumours (38 percent response) and nivolumab in dMMR non-colorectal tumours (36 percent) were positive; most single-agent arms were not. | |
DETERMINE NCT05722886 | platform | Recruiting | Adults, teenagers and children in the United Kingdom with rare cancers, or common cancers carrying rare alterations, matched to licensed targeted drugs and immunotherapies outside their approved indications, with a route to NHS access for arms that work | Recruiting; no arm has reported. | |
CUPISCO NCT03498521 | 2 | Positive | Newly diagnosed unfavourable cancer of unknown primary controlled by three cycles of platinum chemotherapy: randomised to molecularly guided therapy chosen from tissue and blood genomic profiling, or to continued chemotherapy | Median progression-free survival 6.1 months with molecularly guided therapy versus 4.4 months with continued chemotherapy (hazard ratio 0.72); overall survival immature. | |
NAVIGATE NCT02576431 | 2 | Positive | TRK fusion-positive solid tumours in adults and children, any tumour type: larotrectinib single-arm basket trial | ORR 75% by independent review in the first 55 pooled patients across 17 tumour types. | |
| 2 | Recruiting | NAUTIKA1: A Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Multiple Therapies in Biomarker-selected Patients With Resectable Stages IB-III Non-small Cell Lung Cancer | - | ||
| 2 | Recruiting | A Randomized, Multicenter, Open-Label, Phase 2 Study of TRK-950 When Used in Combination With Ramucirumab and Paclitaxel in Patients With Gastric Cancer | - | ||
| 2 | Recruiting | A Phase 2 Study of TL118 for the Treatment of Patients With Solid Tumors Harboring NTRK Gene Fusions | - | - | |
| 2 | Active | An Open-Label, Multicenter, Global Phase 2 Basket Study of Entrectinib for the Treatment of Patients With Locally Advanced or Metastatic Solid Tumors That Harbor NTRK1/2/3, ROS1, or ALK Gene Rearrangements | - | ||
| 2 | Recruiting | A Phase II Study Assessing Safety and Efficacy of Repotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain Metastasis (The REPOSE Study) | - | ||
| 2 | Recruiting | Study to Investigate Outcome of Individualized Treatment Based on Pharmacogenomic Profiling & Ex Vivo Drug Sensitivity Testing of Patient-derived Organoids in Patients With Metastatic Colorectal Cancer | - | ||
| 2 | Active | Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial | - | ||
| 1/2 | Recruiting | A Phase 1/2, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1) | Repotrectinib produced responses in 79 percent of ROS1 inhibitor-naive patients (median progression-free survival 35.7 months) and 38 percent after one ROS1 inhibitor, including 59 percent of those with the G2032R solvent-front mutation. | ||
| 1/2 | Recruiting | A Phase 1/2, Open-Label, Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity Study of Repotrectinib in Pediatric and Young Adult Subjects With Advanced or Metastatic Malignancies Harboring ALK, ROS1, NTRK1-3 Alterations | - | ||
| 1/2 | Recruiting | A Phase I/II Study of TRK-950 in Patients With Advanced Solid Tumors | - | ||
| 1/2 | Active | A Phase 1/2 Study of the Oral TRK Inhibitor Larotrectinib in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors | - | ||
| 1/2 | Active | A Phase 1/2, Open-Label, Dose-Escalation And Expansion Study Of Entrectinib (Rxdx-101) In Pediatrics With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options | - | ||
PROFILE 1001 ROS1 expansion cohort NCT00585195 | 1 | Positive | Advanced ROS1-rearranged non-small-cell lung cancer: crizotinib 250 mg twice daily in an expansion cohort of the phase 1 study, with objective response as the endpoint | Objective response 72 percent (36 of 50); median duration of response 17.6 months; median progression-free survival 19.2 months. |
No recorded escape route names this target.
This KEGG map shows thyroid cancers driven by one relay, the MAPK pathway: RET or NTRK fusions and BRAF mutations in papillary tumours, RAS mutations or PAX8-PPARG fusion in follicular tumours, and TP53 loss marking anaplastic cancer. It matters because RET, NTRK and BRAF alterations each have their own drug, and MAPK blockade can restore iodine uptake.
Which nodes have drugs →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| FoundationOne CDx Foundation Medicine (Roche) · FDA CDx 2017 | NGS tissue | Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase | |
| FoundationOne Liquid CDx Foundation Medicine (Roche) · FDA CDx 2020 | NGS plasma | Per companion claim: EGFR (osimertinib, erlotinib, gefitinib), ALK (alectinib), BRCA1/2 and ATM (olaparib, rucaparib), PIK3CA (alpelisib), FGFR3 (erdafitinib), NTRK and RET; negative plasma results reflex to tissue |
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
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.
The dossier as machine-readable JSON, at /api/v1/dossiers/ntrk.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/ntrk.json. Licence CC BY-NC 4.0.