PI3K / AKT / mTOR
The cell's 'grow and survive' circuit. Growth signals from the surface switch on PI3K, which switches on AKT, which switches on mTOR, which builds proteins and blocks self-destruction.
Receptor tyrosine kinases (HER2, EGFR, IGF1R) activate PI3K (p110α, encoded by PIK3CA), producing PIP3, which recruits AKT. PTEN reverses this step and is a tumour suppressor. AKT phosphorylates many targets including TSC2, releasing mTORC1 to drive protein synthesis, and inhibits FOXO and BAD. The most frequently altered pathway in cancer: PIK3CA mutation (~40% HR+ breast, endometrial, head and neck), PTEN loss (prostate, endometrial, glioblastoma), AKT1 E17K. Drugs: alpelisib, inavolisib (PI3Kα), capivasertib (AKT), everolimus (mTOR), gedatolisib (PI3K/mTOR). Feedback: mTOR inhibition releases AKT, so combinations and endocrine partners are needed.
In one picture
Think of a factory: the receptor is the order desk, PI3K and AKT are the managers relaying the order, PTEN is the accountant cancelling orders, and mTOR is the assembly line. Cancer forges orders (PIK3CA mutation) or fires the accountant (PTEN loss).
Diagram
top- PI3Kα inhibitors (alpelisib, inavolisib) for PIK3CA-mutant HR+ breast cancer
- AKT inhibitor capivasertib for PIK3CA/AKT1/PTEN-altered breast and PTEN-deficient prostate cancer
- mTOR inhibitor everolimus
- Dual PI3K/mTOR gedatolisib (2026)
- Upstream: anti-HER2, anti-EGFR
Pages like this
not linked directly; found by shared links- PathwayRAS / RAF / MEK / ERK (MAPK)
Shares Phosphorylation, Downstream and upstream, mRNA translation (eIF4F / mTOR), Autophagy.
- TechnologySmall-molecule kinase inhibitors
Shares Copanlisib, Duvelisib, Gedatolisib, Umbralisib.
- TermOncogene
Shares Tumour suppressor gene, Growth signal, Hallmark: sustaining proliferative signalling, PIK3CA / PI3K-alpha.
- TermKinase
Shares Phosphorylation, Downstream and upstream, Signalling pathway, Growth signal.
- TermIndication withdrawal
Shares Copanlisib, Duvelisib, Umbralisib, Idelalisib.
- TermGrowth factor
Shares Signalling pathway, Growth signal, Receptor, MET.
- PathwayThe blood–brain barrier & brain metastasis
Shares Capivasertib, AKT, ALK, HER2.
- PathwayResistance routes: how a blocked pathway comes back
Shares BCR::ABL1 (Philadelphia chromosome), BTK (Bruton tyrosine kinase), MET, PIK3CA / PI3K-alpha.