PIK3CA and PIK3R1 mutations in cancer — from the mechanism of activation to PI3K targeted therapies

PIK3CA and PIK3R1 , the genes that encode catalytic (p110α) and regulatory (p85α) subunits of PI3Kα kinase are frequently mutated in cancer patients, resulting in aberrant hyperactivation of the PI3K pathway. Due to its high clinical relevance, mutated PI3K proteins are attractive targets for anti-cancer therapy. To date, some PI3K inhibi­tors have displayed significant therapeutic effects. One of them, alpelisib, has been approved for the treatment of ER-positive, HER2-negative, and PIK3CA -mutated advanced or metastatic breast cancer. Below, we describe how PIK3CA and PIK3R1 mutants influence PI3K activity. We also review the frequency of PIK3CA and PIK3R1 mutations in cancers, diversity of these mutations, and PI3K therapeutic strategies.