# PIK3CA / PI3K-alpha

Source: https://onco.cc/targets/pik3ca/  
OnCo record `pik3ca` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: driver; kinase
- Symbol: PIK3CA
- Class: kinase
- Biology: PIK3CA encodes the catalytic subunit of PI3K; H1047R and E545K are the hotspots.
- Where found: HR+ breast cancer (~40%); Endometrial; Head and neck; Colorectal; Triple-negative breast cancer: mutation (amplification in a further tenth) 10-18%; Colorectal cancer: hotspot mutation (e542k, e545k, h1047r) 20-28%; Gallbladder cancer: mutation about 11%; Non-small-cell lung cancer: hotspot mutation (e545k, e542k, h1047r) 5-7%; Non-small-cell lung cancer: hotspot mutation and high-level amplification 11-38%; Prostate cancer: activating mutation, plus amplification of pik3ca or pik3cb 2-9% depending on disease state

## Notes

- Colorectal cancer: hotspot mutation in 20 to 28% (E545K, H1047R and E542K the commonest), enriched on the right (32.4% against 15.5%) and in mismatch repair deficient tumours (45.2% against 17.6%; cBioPortal). No PI3K or AKT inhibitor is approved in this disease; the interest is as a co-mutation that blunts EGFR antibody benefit and as the basis of the aspirin hypothesis.
- Lung cancer: hotspot mutated in 5 to 7% of adenocarcinomas, where it is usually a passenger alongside a real driver, and in 11 to 16% of squamous tumours with high-level amplification on top in 37.8%, part of the 3q26 gain that also carries SOX2 (cBioPortal). The pathway was altered in 47% of squamous tumours in the founding analysis and has the longest record of failed trials in that histology (Cancer Genome Atlas Research Network 2012).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/P110α
- Wikipedia: https://en.wikipedia.org/wiki/P110α

## Connected records

- biomarkers: [PIK3CA mutation](https://onco.cc/biomarkers/pik3ca-hotspot-mutation/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Erdheim-Chester disease](https://onco.cc/cancers/erdheim-chester-disease/), [Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms](https://onco.cc/cancers/histiocytoses/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [PI3K, AKT and mTOR inhibitors](https://onco.cc/technologies/pi3k-akt-mtor-inhibitors/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Alpelisib](https://onco.cc/drugs/alpelisib/), [Capivasertib](https://onco.cc/drugs/capivasertib/), [Copanlisib](https://onco.cc/drugs/copanlisib/), [Duvelisib](https://onco.cc/drugs/duvelisib/), [Everolimus](https://onco.cc/drugs/everolimus/), [Gedatolisib](https://onco.cc/drugs/gedatolisib/), [Idelalisib](https://onco.cc/drugs/idelalisib/), [Inavolisib](https://onco.cc/drugs/inavolisib/), [Serabelisib](https://onco.cc/drugs/serabelisib/), [Tersolisib](https://onco.cc/drugs/tersolisib/), [therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)](https://onco.cc/drugs/therascreen-cdx/), [Umbralisib](https://onco.cc/drugs/umbralisib/), [Zovegalisib](https://onco.cc/drugs/zovegalisib/)
- companies: [BridgeBio Oncology Therapeutics](https://onco.cc/companies/bridgebio-oncology-therapeutics/), [Cogent Biosciences](https://onco.cc/companies/cogent-biosciences/), [Recursion Pharmaceuticals](https://onco.cc/companies/recursion/), [Relay Therapeutics](https://onco.cc/companies/relay-therapeutics/), [Scorpion Therapeutics](https://onco.cc/companies/scorpion-therapeutics/)
- pathways: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/pathways/bcr-abl1-signalling/), [Breast cancer (KEGG map)](https://onco.cc/pathways/breast-cancer-signalling/), [Cancer metabolism](https://onco.cc/pathways/cancer-metabolism/), [Chemical carcinogenesis - receptor activation](https://onco.cc/pathways/chemical-carcinogenesis-receptor-activation/), [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Endometrial cancer (KEGG map)](https://onco.cc/pathways/endometrial-cancer-signalling/), [FGF / FGFR signalling](https://onco.cc/pathways/fgfr-signalling/), [Gastric cancer (KEGG map)](https://onco.cc/pathways/gastric-cancer-signalling/), [Glioma (KEGG map)](https://onco.cc/pathways/glioma-signalling/), [Intravasation & circulating tumour cells](https://onco.cc/pathways/intravasation-ctc-survival/), [mRNA translation (eIF4F / mTOR)](https://onco.cc/pathways/mrna-translation-eif4f/), [Oestrogen receptor signalling](https://onco.cc/pathways/er-signaling/), [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [Proteoglycans in cancer](https://onco.cc/pathways/proteoglycans-in-cancer/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/), [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/)
- key papers: [Cancer genome landscapes: about 140 driver genes, and each tumour needs only a handful](https://onco.cc/key-papers/paper-vogelstein-cancer-genome-landscapes-science-2013/), [Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial](https://onco.cc/key-papers/paper-schmid-pakt-capivasertib-tnbc-jco-2020/), [Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes](https://onco.cc/key-papers/paper-loree-tumour-location-continuum-colorectal-ccr-2018/), [Clinical sequencing defines the genomic landscape of metastatic colorectal cancer](https://onco.cc/key-papers/paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018/), [Comparison of breast cancer molecular features and survival by African and European ancestry in The Cancer Genome Atlas](https://onco.cc/key-papers/paper-huo-tcga-ancestry-breast-jama-oncol-2017/), [Comprehensive genomic characterization of squamous cell lung cancers](https://onco.cc/key-papers/paper-tcga-lung-squamous-nature-2012/), [Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention](https://onco.cc/key-papers/paper-giraldo-gallbladder-msk-impact-ccr-2022/), [Comprehensive molecular characterization of human colon and rectal cancer](https://onco.cc/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/), [Comprehensive molecular portraits of human breast tumours](https://onco.cc/key-papers/paper-tcga-breast-molecular-portraits-nature-2012/), [EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes](https://onco.cc/key-papers/paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019/), [Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies](https://onco.cc/key-papers/paper-jiang-fuscc-tnbc-landscape-cancer-cell-2019/), [Population-Specific Immunogenomic Alterations in Gallbladder Cancer and Prognostic Significance](https://onco.cc/key-papers/paper-zhu-population-specific-immunogenomics-gallbladder-cancer-mod-pathol-2025/), [Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours](https://onco.cc/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/), [Reciprocal feedback regulation of PI3K and androgen receptor signalling in PTEN-deficient prostate cancer](https://onco.cc/key-papers/paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011/), [Regional differences in gallbladder cancer pathogenesis: insights from a multi-institutional comparison of tumor mutations](https://onco.cc/key-papers/paper-narayan-gallbladder-regional-mutations-cancer-2019/), [SU2C-PCF: integrative clinical genomics of advanced prostate cancer](https://onco.cc/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/), [TCGA: the molecular taxonomy of primary prostate cancer](https://onco.cc/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/), [The clonal and mutational evolution spectrum of primary triple-negative breast cancers](https://onco.cc/key-papers/paper-shah-tnbc-clonal-evolution-nature-2012/), [Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis](https://onco.cc/key-papers/paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018/), [Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs](https://onco.cc/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/)
- trials: [ALASCCA](https://onco.cc/trials/alascca/), [CAPItello-291](https://onco.cc/trials/capitello-291/), [Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC](https://onco.cc/trials/nct03997123/), [INAVO120](https://onco.cc/trials/inavo120/), [IPATunity130](https://onco.cc/trials/ipatunity130/), [LOTUS](https://onco.cc/trials/lotus/), [PAKT](https://onco.cc/trials/pakt/), [SOLAR-1](https://onco.cc/trials/solar-1/)
- terms: [Endocrine resistance](https://onco.cc/terms/endocrine-resistance/), [Hallmark: sustaining proliferative signalling](https://onco.cc/terms/sustaining-proliferative-signaling/), [Oncogene](https://onco.cc/terms/oncogene/), [PTEN loss](https://onco.cc/terms/pten-loss/)
- pairings: [PI3K/AKT-pathway inhibitor + endocrine therapy (± CDK4/6)](https://onco.cc/pairings/pi3k-pathway-plus-endocrine/)
- people: [Fabrice André](https://onco.cc/people/fabrice-andre/), [Komal Jhaveri](https://onco.cc/people/komal-jhaveri/), [Ramon E. Parsons](https://onco.cc/people/ramon-parsons/), [Yardena Samuels](https://onco.cc/people/yardena-samuels/)
- ideas: [Get biomarker-directed aspirin after colorectal surgery into labels and guidelines](https://onco.cc/ideas/idea-reg-aspirin-pik3ca-implementation/)
- institutions: [Vanderbilt-Ingram Cancer Center](https://onco.cc/institutions/vanderbilt-ingram/)

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JSON: https://onco.cc/api/v1/entities/pik3ca.json