Loading
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.
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.
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.
Alpelisib was the first PI3K drug for PIK3CA-mutant breast cancer (2019). It is effective, but high blood sugar and rash limited its use, and newer drugs are displacing it.
Capivasertib (Truqap) is the first AKT inhibitor, for breast cancer with PI3K-pathway mutations and, since 2026, for prostate cancer with PTEN loss.
An mTOR-blocking pill that doubled progression-free time with exemestane in 2012 and is now paired with the oral SERD giredestrant.
Inavolisib is a PI3K drug that also destroys the mutant protein, approved in 2024 with palbociclib and fulvestrant for PIK3CA-mutant breast cancer.
A weekly infusion that was the first drug to extend survival in poor-risk kidney cancer (2007), and in 2024 the first targeted drug to improve outcomes in childhood rhabdomyosarcoma.
Query for this technology: (TITLE:"PI3K, AKT and mTOR inhibitors" OR ABSTRACT:"PI3K, AKT and mTOR inhibitors") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PI3K, AKT and mTOR inhibitors, not a curated reading list.
Shares A Phase IIIB Study to Evaluate the Use of Capivasertib in Combination With Fulvestrant in Patients With Advanced Breast Cancer Who Have Relapsed/Progressed on ET and CDK4/6 Inhibitor Reflecting Real World Clinical Practice in Spain, Capivasertib+Fulvestrant asTreatment for Locally Advanced(Inoperable) or Metastatic HR+/HER2- Breast Cancer in Chinese Patients, To Study the Effect of Inavolisib in Combination With Fulvestrant in Participants With Breast Cancer, Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant in Japanese Men and Postmenopausal Women With Advanced Breast Cancer.
Shares A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy, Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-positive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor., BOLERO-2, CAPItello-291.
Shares Inavolisib, Alpelisib, AKT, Capivasertib.
Shares Inavolisib, Alpelisib, AKT, Capivasertib.
Shares A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer, A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer, A Study to Test Inavolisib Treatments in Participants With Early-Stage, PIK3CA-Mutated Breast Cancer, To Study the Effect of Inavolisib in Combination With Fulvestrant in Participants With Breast Cancer.
Shares Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation., Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant in Japanese Men and Postmenopausal Women With Advanced Breast Cancer, Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Chinese Men and Postmenopausal Women With Advanced Breast Cancer, Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation.
Shares CAPItello-281, LOTUS, IPATunity130, PAKT.
Shares Temsirolimus, mTOR, Everolimus, Renal cell carcinoma.