ROS1
A gene fusion in about 1-2% of lung cancers that responds for years to targeted pills, now in their third generation.
ROS1 rearrangements (CD74-ROS1 most common) occur in ~1-2% of NSCLC, typically in younger never-smokers. Crizotinib (2016) and entrectinib (2019) were first; repotrectinib (2023) covers the G2032R solvent-front mutation; zidesamtinib (July 2026) adds TRK sparing to reduce neurologic toxicity. Also seen in cholangiocarcinoma and glioblastoma (rare).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A gene fusion in about 1-2% of lung cancers that responds for years to targeted pills, now in their third generation.
- 1 · What it is
A gene fusion in about 1-2% of lung cancers that responds for years to targeted pills, now in their third generation.
- 2 · What goes wrong in cancer
Receptor tyrosine kinase with homology to ALK; fusions constitutively activate MAPK, PI3K, and JAK-STAT.
- 3 · How drugs use it
4 products aim at ROS1: 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
Receptor tyrosine kinase with homology to ALK; fusions constitutively activate MAPK, PI3K, and JAK-STAT.
- NSCLC (~1-2%)
- Cholangiocarcinoma, glioblastoma, Spitz tumours (rare)
Crizotinib was the first ALK inhibitor, approved four years after ALK fusions were found in lung cancer; it was also the first drug for ROS1 lung cancer and for ALK-positive lymphoma and inflammatory myofibroblastic tumour in children.
Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.
A ROS1 and NTRK pill that also works after other ROS1 drugs fail, with dizziness as its signature side effect.
A ROS1 lung-cancer pill approved in 2025 that works in the brain and after crizotinib, with fewer dizziness-type side effects than repotrectinib.
Latest papers
topQuery for this target: (TITLE:"ROS1" OR ABSTRACT:"ROS1") 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 ROS1, not a curated reading list.
Pages like this
not linked directly; found by shared links- TargetALK
Shares Dong-Wan Kim, LUNGevity Foundation (and GO2 for Lung Cancer), On-target resistance mutations (gatekeeper, solvent-front, compound), University of Colorado Cancer Center and the tags driver, kinase.
- TargetRET
Shares Alexander Drilon, Koichi Goto, Sequence: targeted therapy before immunotherapy in driver-positive NSCLC, Receptor tyrosine kinase activation and the tags driver, kinase.
- TargetFGFR2
Shares Receptor tyrosine kinase activation, PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
- TargetKIT
Shares Receptor tyrosine kinase activation, PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK) and the tags driver, kinase.
- TargetEGFR
Shares LUNGevity Foundation (and GO2 for Lung Cancer), On-target resistance mutations (gatekeeper, solvent-front, compound), Sequence: targeted therapy before immunotherapy in driver-positive NSCLC, Receptor tyrosine kinase activation and the tags driver, kinase.
- TargetPIK3CA / PI3K-alpha
Shares Receptor tyrosine kinase activation, PI3K / AKT / mTOR and the tags driver, kinase.
- TargetFLT3
Shares Receptor tyrosine kinase activation and the tags driver, kinase.
- TargetBRAF
Shares RAS / RAF / MEK / ERK (MAPK), Non-small-cell lung cancer and the tags driver, kinase.