Dissecting "PI3Kness": The Complexity of Personalized Therapy for Ovarian Cancer

Epithelial ovarian cancers exhibit marked heterogeneity and can be divided into low-grade type I and more prevalent high-grade type II lesions that differ in stage at diagnosis, rate of growth, and susceptibility to platinum-based chemotherapy. Activation of the phosphatidylinositol 3' inase (PI3K) pathway occurs in a significant fraction of both types of ovarian cancer, driven predominantly by mutations in type I and amplification in type II. Available cell lines do not often reflect the genotype of type II ovarian cancers, but studies with cell lines driven by mutation suggest that blocking activated AKT is necessary, but not sufficient to inhibit cancer cell growth. Inhibition of multiple signaling pathways will likely be required to achieve effective personalized therapy for patients whose cancers exhibit "PI3Kness." Cancer Discovery; 2(1); 16-8. (C) 2012 AACR.