Kinase and phosphatase inhibition as a signal transduction-centric approach to adjunctive chemotherapies for the treatment of gynecologic cancers: PPP1CA.

Men and women differ in large part resulting from the presence or absence of gynecologic organs including the ovaries, the uterus, the lining of which is known as the endometrium, and the entry to the uterus (womb), the cervix (1), all of which are targets for development of malignancies (2-7); vulvar cancer is less common (8). Cancer, or unrestricted cell division which develops into a tumor after remaining unchecked, evades active cell death and cell cycle control mechanisms, sustaining its survival through growth factor signals (9) which are transduced to the nucleus to activate and repress transcription of genes (10, 11). These signals are transduced between the plasma membrane and the nucleus by the action of kinases and phosphatases, enzymes that utilize conformational changes and a catalytic site to translate a signal from the extracellular environment to a change in gene expression. Catalytic sites are pharmacologically targetable, and small molecule targeting of the appropriate kinase or phosphatase target will disrupt or block this transduction (12, 13). We utilized whole transcriptome technologies (14, 15) to identify and validate kinase and phosphatase targets in gynecologic oncology, including cancer of the ovary, or epithelial ovarian cancer. Here we describe a differentially expressed, up-regulated, and catalytically available phosphatase target in epithelial ovarian cancer: PPP1CA.