Targeting PI3K Mutations

    • PIK3CA are the most common mutations in class I PI3K genes. Missense mutations occur in all domains of p110α, with most in the “hotspots” E542K, E545K (both in the exon 9—helical domain), and H1047R (in exon 20—the kinase domain) and confer constitutive activation of p110α.
    • In PIK3R1, most mutations are substitutions or in-frame insertions or deletions in the inter-SRC homology 2 domain (iSH2 domain) of p85α, the region that contacts with p110. They enhance PI3K activity. PIK3R1 somatic mutations are prevalent in endometrial cancer, glioma, and colon cancer. In addition, ncers present with reduced expression of PIK3R1.
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