driver

ALK is a gene fusion driver in about 4 to 5% of non-small-cell lung cancers that responds to a succession of ALK inhibitor pills. Lorlatinib kept about 60% of patients progression-free at five years, alectinib is approved after surgery, and neladalkib targets compound resistance mutations.

The fusion that defines chronic myeloid leukaemia and a quarter of adult acute lymphoblastic leukaemia; the first cancer driver ever switched off by a pill.

BRAF is a signalling kinase mutated in half of melanomas; blocking it with two drugs at once became a template for targeted therapy.

A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.

FGFR2 is a growth receptor fused in bile-duct cancer and overproduced in gastric cancer.

FLT3 is a kinase mutated in about a third of acute myeloid leukaemias, where adding an inhibitor to chemotherapy improves survival.

A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.

A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias.

KIT mutation is the driver behind most gastrointestinal stromal tumours, and the reason imatinib turned a sarcoma with a median survival of about a year into a chronic disease.

A gene fusion that drives an aggressive leukaemia in infants and adults. It cannot be blocked directly, but the scaffold protein it depends on (menin) can.

KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.

A receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail.

NPM1 is the most common mutation in adult leukaemia. It moves a nuclear protein into the cytoplasm and, it turns out, makes the leukaemia dependent on menin.

Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it.

PIK3CA is the most commonly mutated gene in hormone-driven breast cancer. Drugs against it work, but hitting it cleanly without raising blood sugar took years.

RET is a kinase altered in thyroid cancer and a small slice of lung cancer, treatable with one selective pill regardless of where the tumour is.

A gene fusion in about 1-2% of lung cancers that responds for years to targeted pills, now in their third generation.