Breast and ovarian cancers exhibit similar epidemiologic, genotypic, and phenotypic characteristics. Phosphatidylinositol 3-kinase (P13K) and the PTEN tumor suppressor gene product phosphorylate and dephosphorylate the same 3′ site in the inositol ring of membrane phosphatidylinositols. Germ-line mutations in the PTEN tumor suppressor gene are causative of Cowden's breast cancer predisposition syndrome, and PTEN is frequently mutated in sporadic breast cancers. In contrast, amplification of multiple components of the P13K pathway is a hallmark of serous epithelial ovarian cancers. The resultant activation of the P13K pathway in both breast and ovarian cancers contributes to cell-cycle progression, decreased apoptosis, and increased metastatic capabilities. Strikingly, both ovarian and breast cancer cells are selectively sensitive to pharmacologic and genetic manipulation of the P13K pathway, making molecular therapeutics targeting this pathway particularly attractive approaches for these cancers.
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