{"entity":{"id":"pi3k-akt-mtor-inhibitors","kind":"technology","name":"PI3K, AKT and mTOR inhibitors","aka":[],"tldr":"Drugs against one of the most commonly mutated growth pathways in cancer, now used with hormone therapy in breast cancer and in kidney and neuroendocrine tumours, with high blood sugar as the shared side effect.","summary":"The PI3K-AKT-mTOR pathway is altered in a large share of tumours. Rapalogues (everolimus, temsirolimus) were approved first, for kidney cancer and later breast and neuroendocrine tumours. Alpelisib (PIK3CA-mutant breast cancer, 2019), capivasertib (an AKT inhibitor, 2023) and inavolisib (a PI3K-alpha degrader-like inhibitor, 2024) followed in hormone receptor-positive breast cancer with fulvestrant. Hyperglycaemia, rash and stomatitis limit dosing, and mutant-selective PI3K-alpha inhibitors aim to spare wild-type enzyme.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway"}],"tags":[],"related":[],"cancers":["breast-hr-positive","rcc"],"sections":["targeted-therapy"],"technologies":[],"targets":["pik3ca","akt","mtor"],"drugs":["everolimus","temsirolimus","alpelisib","capivasertib","inavolisib"],"companies":["mei-pharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"ATP-competitive or allosteric inhibitors block PI3K catalytic subunits, AKT or mTORC1, cutting the survival and growth signalling downstream of receptor tyrosine kinases and PIK3CA mutations.","strengths":["Approved in several diseases","Combination with endocrine therapy extends control in breast cancer","Biomarker-selected use"],"limitations":["Hyperglycaemia and rash limit doses","Feedback activation blunts single-agent effect","Modest survival gains"],"since":2009},"route":"/technologies/pi3k-akt-mtor-inhibitors/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"target":[{"id":"akt","kind":"target","name":"AKT","route":"/targets/akt/"},{"id":"mtor","kind":"target","name":"mTOR","route":"/targets/mtor/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / 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