Composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit, Phosphatidylinositol 3-kinase has been found to be oncogenic and has been implicated in cervical cancers. PIK3CA is the most commonly mutated gene in HR+/HER2- advanced breast cancer1. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2.
PIK3CA Gene Methylation
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40% of patients with HR+/HER2-advanced breast cancer have PIK3CA mutation1
PIK3CA is the most commonly mutated gene in breast cancer, and it has been linked to a variety of cancers. The 542/545 area of the helical domain and the 1047 region of the kinase domain have long been recognized as hotspots for activating mutations in PIK3CA, which is a key element of the PI3K pathway. PIK3CA and its interactions with the AKT and mTOR pathways have sparked a lot of study and development, and PI3K inhibition has had some limited success in clinical trials recently. While monotherapies appear to have limited efficacy, there has recently been renewed interest in using PI3K inhibition as part of a combination therapy approach.
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1. The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature.2012;490(7418):61-70.