Driver mutation (actionable / targetable alteration)
A genetic change that actually pushes the cancer to grow, as opposed to the many harmless 'passenger' mutations along for the ride. When a drug exists that blocks it, the driver is called actionable.
Cancers carry thousands of mutations but usually depend on a handful of drivers (EGFR, ALK, KRAS, BRAF, HER2, RET, ROS1, MET, NTRK in lung cancer; BRAF in melanoma; KIT in GIST). Comprehensive genomic profiling looks for them, and matching a driver to its inhibitor gives response rates of 60-80% versus 20-30% for chemotherapy, at the cost of eventual acquired resistance. 'Driver-negative' lung cancer is treated with chemo-immunotherapy instead. Actionability is tiered (ESCAT, OncoKB levels) from approved companion-diagnostic pairs to investigational targets, and tumour-agnostic approvals (NTRK, BRAF V600E, RET) reward drivers regardless of organ.
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