Small-molecule tyrosine kinase inhibitors
How tyrosine kinase inhibitors bind their targets, why resistance mutations such as T315I and T790M arise, the class toxicities that follow from each target, and the absorption and CYP3A4 interactions that change exposure.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- TKIs are oral small molecules ("-tinib") that block the ATP-binding pocket (or an allosteric site) of a kinase driven by a mutation, fusion or amplification.
- They work only when the tumour is addicted to that driver: BCR-ABL in CML, EGFR exon 19 deletion or L858R and ALK fusions in NSCLC, BRAF V600 in melanoma, KIT in GIST.
- Resistance is predictable: gatekeeper mutations (T315I, T790M), covalent-site mutations (C797S, BTK C481S), bypass signalling (MET amplification) or histological change (NSCLC to small cell).
Loading the rest of the note…
Finished reading?
Sources
- eviQ cancer treatmentsAU/NZCancer Institute NSW, 2026
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)Annals of Oncology (Mateo et al., 2018;29:1895-902), 2018
- The ESMO Scale for Clinical Actionability of Molecular Targets, version 2 (ESCAT v2)Annals of Oncology (El Helali et al., 2026), 2026
- Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer (FLAURA)New England Journal of Medicine (Soria et al., 2018;378:113-25), 2018
- Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failureNew England Journal of Medicine (Hughes et al., 2019;381:2315-26), 2019
- Last updated
- 14 November 2026
What changed
- 14 November 2026 Turnstile bot check on sign-in and signed-out feedback