ALK and ROS1 inhibitors
Oral kinase inhibitors for lung cancers driven by an ALK or ROS1 gene fusion, found by testing the tumour.
What they are
Small molecules that block the ALK receptor tyrosine kinase, and several also ROS1. Crizotinib was the first; alectinib, brigatinib, ceritinib and lorlatinib are newer, more selective agents that have largely replaced it in ALK-positive non-small cell lung cancer.
Mechanism of action
A chromosomal rearrangement can fuse ALK to a partner gene (most often EML4 in lung cancer), producing a kinase that is always switched on and drives growth. ROS1 fusions behave the same way. These drugs occupy the ATP pocket of the fused kinase, so its growth and survival signals stop. Resistance comes from new mutations in the kinase domain, which the newer generations were designed to overcome.
Target: ALK and ROS1 receptor tyrosine kinases (fusion proteins such as EML4-ALK)
Drugs in this class
- CrizotinibThe first ALK inhibitor: an oral drug for ALK- or ROS1-positive lung cancer that also blocks MET. Watch the eyes, the…ALK receptor tyrosine kinase (also ROS1 and MET)
- AlectinibA selective second-generation ALK inhibitor for ALK-positive lung cancer, also after surgery. Watch muscles, liver…ALK receptor tyrosine kinase
- LorlatinibA third-generation ALK and ROS1 inhibitor for ALK-positive lung cancer, first line or after other ALK drugs. Watch…ALK and ROS1 receptor tyrosine kinases
Others in the class
- ceritinib
- brigatinib
Test yourself
Think of the answer, then tap the question to see it.
Which gene fusion is the classic target of ALK inhibitors in lung cancer?
EML4-ALK, a fusion that keeps the ALK kinase permanently active.
Which ALK inhibitor was first developed against MET?
Crizotinib; it also inhibits ROS1.
Why are newer ALK inhibitors used after crizotinib fails?
They remain active against several ALK mutations that make the tumour resistant to crizotinib.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Crizotinib - NCI (National Cancer Institute, 2022).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.