PIK3CA / PI3K-alpha
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.
PIK3CA mutations occur in ~40% of HR+ breast cancer. Alpelisib (SOLAR-1), inavolisib (INAVO120, mutant-selective, with palbociclib and fulvestrant), and capivasertib (AKT) are approved. Gedatolisib (pan-PI3K/mTOR, Revtorpyk) was approved in 2026. Mutant-selective and allosteric inhibitors (RLY-2608) aim to avoid hyperglycaemia.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
PIK3CA encodes the catalytic subunit of PI3K; H1047R and E545K are the hotspots.
- 3 · How drugs use it
9 products aim at PIK3CA / PI3K-alpha: small molecules and degraders. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Biology
PIK3CA encodes the catalytic subunit of PI3K; H1047R and E545K are the hotspots.
- HR+ breast cancer (~40%)
- Endometrial
- Head and neck
- Colorectal
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Endometrial cancer | 45-55% | Activating mutation | cBioPortal (TCGA) | |
| HR-positive / HER2-negative breast cancer | 35-40% | Activating mutation | cBioPortal (TCGA) | |
| Head and neck squamous cell carcinoma | 15-20% | Activating mutation | HPV+ enriched | cBioPortal (TCGA) |
| Colorectal cancer | 15-20% | Activating mutation | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
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.
Copanlisib is an intravenous PI3K inhibitor for relapsed follicular lymphoma, approved in 2017 and withdrawn in 2023 when its confirmatory trial failed.
A dual PI3K inhibitor for relapsed CLL whose survival data raised FDA concern; use is now limited to late lines.
An mTOR-blocking pill that doubled progression-free time with exemestane in 2012 and is now paired with the oral SERD giredestrant.
An intravenous drug that blocks the whole PI3K/mTOR pathway, approved in July 2026 for hormone-positive breast cancer.
Idelalisib was the first PI3K inhibitor for blood cancers; it is effective in CLL with rituximab but so toxic (colitis, hepatitis, pneumonitis, infections) that the class has largely been abandoned.
Inavolisib is a PI3K drug that also destroys the mutant protein, approved in 2024 with palbociclib and fulvestrant for PIK3CA-mutant breast cancer.
A PI3K inhibitor for marginal zone and follicular lymphoma approved in 2021 and withdrawn in 2022 after the UNITY-CLL trial suggested more deaths.
Latest papers
topQuery for this target: (TITLE:"PIK3CA / PI3K-alpha" OR ABSTRACT:"PIK3CA / PI3K-alpha" OR TITLE:"PIK3CA" OR ABSTRACT:"PIK3CA") 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 PIK3CA / PI3K-alpha, not a curated reading list.
Pages like this
not linked directly; found by shared links- TargetALK
Shares Oncogene, Hallmark: sustaining proliferative signalling, Resistance routes: how a blocked pathway comes back, Receptor tyrosine kinase activation and the tags driver, kinase.
- TargetEGFR
Shares Vanderbilt-Ingram Cancer Center, Oncogene, Hallmark: sustaining proliferative signalling, Resistance routes: how a blocked pathway comes back and the tags driver, kinase.
- TargetBRAF
Shares Oncogene, Cancer genome landscapes: about 140 driver genes, and each tumour needs only a handful, Hallmark: sustaining proliferative signalling, Small-molecule kinase inhibitors and the tags driver, kinase.
- TargetFGFR2
Shares Receptor tyrosine kinase activation, PI3K / AKT / mTOR, Small-molecule kinase inhibitors and the tags driver, kinase.
- TargetKIT
Shares Receptor tyrosine kinase activation, PI3K / AKT / mTOR, Small-molecule kinase inhibitors and the tags driver, kinase.
- TargetROS1
Shares Receptor tyrosine kinase activation, PI3K / AKT / mTOR and the tags driver, kinase.
- TargetFLT3
Shares Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.
- TargetRET
Shares Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.