tyrosine kinase inhibitor

A tyrosine kinase inhibitor, often shortened to TKI, switches off a kind of cellular on-switch that tells cells to grow. A tyrosine kinase is an enzyme that flips a signal to ON by attaching a phosphate tag to other proteins. In many cancers one of these switches is stuck permanently ON, driving relentless growth. A TKI jams the switch back OFF.

Most TKIs are small molecules taken as pills that slip into the kinase's ATP-binding pocket, the slot where the enzyme grabs the energy it needs to add phosphate. By occupying that pocket they block the reaction. Different TKIs are tuned to different kinases, such as BCR-ABL in chronic myeloid leukaemia, EGFR in some lung cancers, or VEGFR in tumours that drive blood-vessel growth. They are a major category of targeted therapy.

Because they are taken orally and depend on a present target, TKIs require the right molecular match and good adherence. Resistance is common: a tumour can acquire a new mutation in the kinase pocket that prevents the drug from binding, which is why later-generation TKIs were designed to overcome specific resistance mutations. Side effects depend on which kinases are hit and can include rash, diarrhoea, liver effects and high blood pressure.