NTRK
Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it.
NTRK fusions are rare (<1% of common cancers, near-universal in infantile fibrosarcoma and secretory carcinoma). Larotrectinib and entrectinib were the first tumour-agnostic kinase inhibitor approvals (2018-2019). Repotrectinib addresses resistance mutations.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it.
- 2 · What goes wrong in cancer
NTRK1/2/3 encode the neurotrophin receptor kinases TrkA, TrkB and TrkC.
- 3 · How drugs use it
3 products aim at NTRK: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Biology
NTRK1/2/3 encode the neurotrophin receptor kinases TrkA, TrkB and TrkC.
- Infantile fibrosarcoma
- Secretory breast/salivary carcinoma
- Thyroid, colorectal, lung (rare)
How common it is, by cancer
| 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 |
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.
Latest papers
topQuery 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.
Pages like this
not linked directly; found by shared links- TargetRET
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, Alexander Drilon, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling and the tag driver.
- TargetROS1
Shares Repotrectinib, Alexander Drilon, University of Colorado Cancer Center, Entrectinib and the tag driver.
- TargetBRAF
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, Cancer of unknown primary (CUP) and the tag driver.
- TargetKRAS
Shares Receptor tyrosine kinase activation, RAS / RAF / MEK / ERK (MAPK), Small-molecule kinase inhibitors, Pancreatic ductal adenocarcinoma and the tag driver.
- TargetALK
Shares University of Colorado Cancer Center, Entrectinib, Gene fusion, Receptor tyrosine kinase activation and the tag driver.
- TargetFGFR2
Shares Gene fusion, Receptor tyrosine kinase activation, RAS / RAF / MEK / ERK (MAPK), Biliary tract cancer (cholangiocarcinoma) and the tag driver.
- TargetKIT
Shares Gastrointestinal stromal tumour (GIST), Receptor tyrosine kinase activation, RAS / RAF / MEK / ERK (MAPK), Sarcomas (soft tissue, bone, GIST) and the tag driver.
- TermTumour-agnostic (tissue-agnostic) approval
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, Larotrectinib.