Kinase inhibitors (targeted oncology)
Oral cancer drugs that block a kinase the tumour depends on, such as BCR-ABL in CML or mutant EGFR in lung cancer.
What they are
Small molecules, taken by mouth, that inhibit protein kinases driving a tumour: BCR-ABL (imatinib, dasatinib, nilotinib), EGFR (erlotinib, gefitinib, afatinib, osimertinib), BTK (ibrutinib), mutant BRAF (vemurafenib) and several angiogenic kinases (sorafenib). They work best when a test shows the tumour carries the target.
Mechanism of action
Most compete with ATP in the kinase's catalytic pocket, so the enzyme cannot phosphorylate its substrates and the growth and survival signal stops. Some bind covalently to a cysteine near the pocket (afatinib, osimertinib, ibrutinib) and inhibit irreversibly. Tumours escape through new mutations in the kinase (for example T315I in BCR-ABL or T790M in EGFR) or by switching to other pathways.
Target: Protein kinases (BCR-ABL, EGFR, BTK, BRAF, VEGFR)
Drugs in this class
- ImatinibThe first targeted kinase inhibitor: it shuts down BCR-ABL in Philadelphia-positive CML and KIT in GIST. Typical…BCR-ABL tyrosine kinase (ABL1 kinase domain)
- DasatinibA second-generation BCR-ABL and SRC inhibitor for CML and Ph-positive ALL, including after imatinib failure; known for…BCR-ABL tyrosine kinase (ABL1 kinase domain); also SRC-family kinases
- ErlotinibA reversible EGFR kinase inhibitor for lung cancer with EGFR exon 19 or L858R mutations, and for pancreatic cancer…EGFR tyrosine kinase domain
- AfatinibA second-generation, irreversible inhibitor of EGFR, HER2 and HER4 for EGFR-mutant lung cancer; diarrhoea and rash are…EGFR tyrosine kinase domain
- GefitinibA first-generation, reversible EGFR kinase inhibitor for lung cancer with EGFR exon 19 deletion or L858R mutation…EGFR tyrosine kinase domain
- IbrutinibOral covalent BTK inhibitor that switches off B-cell receptor signalling in CLL and Waldenström macroglobulinaemia…Bruton tyrosine kinase (BTK)
- NilotinibA second-generation BCR-ABL inhibitor for CML. It prolongs the QT interval (boxed warning) and must be taken on an…BCR-ABL tyrosine kinase (ABL1 kinase domain)
- OsimertinibA third-generation, irreversible EGFR inhibitor active against the T790M resistance mutation; now a standard…EGFR tyrosine kinase domain
- SorafenibAn oral multikinase inhibitor (RAF, VEGFR, PDGFR) for liver, kidney and iodine-refractory thyroid cancer; hand-foot…VEGFR2 and other kinases (CRAF, BRAF, VEGFR1–3, PDGFR-β, KIT, FLT3, RET)
- VemurafenibAn oral inhibitor of mutant BRAF V600E for melanoma that carries this mutation; it causes photosensitivity and new…BRAF kinase with the V600E mutation
- AsciminibA BCR-ABL inhibitor that binds outside the ATP site (the myristoyl pocket); works in chronic myeloid leukaemia…BCR-ABL1 tyrosine kinase (myristoyl pocket of ABL1)
- BosutinibSecond-generation BCR-ABL and SRC kinase inhibitor taken by mouth for Ph-positive CML. Diarrhoea is its hallmark; it…BCR-ABL tyrosine kinase (ABL1 kinase domain); also SRC-family kinases
- PonatinibThird-generation BCR-ABL inhibitor that also blocks the T315I mutant. Reserved for resistant CML and Ph-positive ALL…BCR-ABL tyrosine kinase (ABL1 kinase domain), including the T315I gatekeeper mutant
- AcalabrutinibSecond-generation covalent BTK inhibitor, more selective than ibrutinib, taken twice a day for CLL, small lymphocytic…Bruton's tyrosine kinase (BTK)
Others in the class
- bosutinib
- ponatinib
- lapatinib
- dabrafenib
- trametinib
- sunitinib
- acalabrutinib
Test yourself
Think of the answer, then tap the question to see it.
Which mutation makes BCR-ABL resistant to imatinib, dasatinib and nilotinib?
T315I, the «gatekeeper» mutation in the ABL kinase domain; ponatinib is active against it.
Why is an EGFR kinase inhibitor chosen only after testing the lung tumour?
Because the benefit is in tumours with activating EGFR mutations (exon 19 deletion or L858R).
Which enzyme metabolises most of these drugs, making them prone to interactions?
CYP3A4.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - IMATINIB MESYLATE- imatinib tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - ERLOTINIB tablet, film coated (DailyMed (U.S. National Library of Medicine), 2022); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.