Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies

Abstract

Recent developments in genomic analysis have unveiled the key signaling pathways in human cancer. However, only a limited number of molecular-targeted drugs are applicable for clinical use in gynecologic malignancies. TP53 signaling and phosphatidylinositol 3 kinase pathways are frequently mutated in cancer, and have received much attention as molecular targets in human cancers. In this review, we mainly focus on the functions of these pathways, and discuss the molecular-targeted drugs under clinical trials. The molecular-targeted drugs described in this review include dual phosphatidylinositol 3 kinase/mTOR inhibitors (NVP-BEZ235, DS-7423, SAR245409), an mTOR inhibitor (everolimus), an MEK inhibitor (pimasertib), an autophagy inhibitor (chloroquine), a cyclin-dependent kinases 4/6 inhibitor (PD0332991), and a poly (ADP-ribose) polymerase inhibitor (olaparib).

Keywords: TP53; endometrial cancer; molecular target therapy; ovarian clear cell carcinoma; phosphatidylinositol 3 kinase.