Platelet-derived growth factor pathway inhibitors in ovarian cancer

Platelet-derived growth factor receptors (PDGFRs) are expressed in 50%-70% of ovarian tumors. Platelet-derived growth factor receptor is present and activated in tumor cells through paracrine and autocrine mechanisms. Normal cells in the stroma, particularly fibroblasts, pericytes, and endothelial cells, also harbor PDGFR. The PDGF-PDGFR pathway governs cancer cell proliferation and survival. Platelet-derived growth factor also modulates the stroma, controls tissue interstitial pressure, and plays a role in angiogenesis. Thus, the use of PDGFR inhibitors as cancer therapeutic agents translates into direct inhibitory effects on tumor cells' growth and indirect effects on the stroma. These effects might include increased delivery of chemotherapy into tumors and antiangiogenic properties induced partly by disruption of the pericytes' function. Imatinib mesylate, sorafenib, dasatinib, sunitinib, and neutralizing PDGFR antibodies are being investigated in clinical trials in patients with recurrent ovarian cancer. Development of molecular predictors of activity should remain a priority during early clinical development.