{"slug":"driver","tag":"driver","variants":["driver"],"description":"Targets that are driver alterations of a cancer.","count":17,"kinds":{"target":17},"related":[{"slug":"kinase","tag":"kinase","shared":11},{"slug":"adc-target","tag":"adc-target","shared":2},{"slug":"fusion","tag":"fusion","shared":2},{"slug":"epigenetic","tag":"epigenetic","shared":1},{"slug":"mrd-marker","tag":"mrd-marker","shared":1},{"slug":"tumour-agnostic","tag":"tumour-agnostic","shared":1}],"records":[{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/","tldr":"A gene fusion in about 1-2% of lung cancers that responds for years to targeted pills, now in their third generation."},{"id":"kmt2a","kind":"target","name":"KMT2A (MLL) rearrangement","route":"/targets/kmt2a/","tldr":"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."},{"id":"npm1","kind":"target","name":"NPM1 mutation","route":"/targets/npm1/","tldr":"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."},{"id":"bcr-abl","kind":"target","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/targets/bcr-abl/","tldr":"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."},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/","tldr":"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."},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/","tldr":"A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills."},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/","tldr":"KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021."},{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/","tldr":"BRAF is a signalling kinase mutated in half of melanomas; blocking it with two drugs at once became a template for targeted therapy."},{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/","tldr":"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."},{"id":"met","kind":"target","name":"MET","route":"/targets/met/","tldr":"A receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail."},{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/","tldr":"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."},{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/","tldr":"Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it."},{"id":"fgfr2","kind":"target","name":"FGFR2","route":"/targets/fgfr2/","tldr":"FGFR2 is a growth receptor fused in bile-duct cancer and overproduced in gastric cancer."},{"id":"kit","kind":"target","name":"KIT","route":"/targets/kit/","tldr":"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."},{"id":"flt3","kind":"target","name":"FLT3","route":"/targets/flt3/","tldr":"FLT3 is a kinase mutated in about a third of acute myeloid leukaemias, where adding an inhibitor to chemotherapy improves survival."},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/","tldr":"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."},{"id":"idh","kind":"target","name":"IDH1 / IDH2","route":"/targets/idh/","tldr":"A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias."}]}