Investigational agents in development for the treatment of ovarian cancer.
Although significant success has been achieved in the treatment of advanced and recurrent ovarian cancer, there is clearly room for improvement. The use of targeted agents in this patient population has the promise to provide improved survival and quality of life. There are a myriad of relevant pathways under exploration in all settings of ovarian cancer. Clinical trial data are accumulating for antiangiogenic therapy, including vascular endothelial growth factor (VEGF)-specific inhibitors and multiple angiogenic signaling target inhibitors, as well as poly-ADP-ribose polymerase (PARP) inhibitors. Other types of tumorigenic pathway inhibitors, including those that target phosphatidylinositol-3-kinase (PI3K), mammalian target of rapamycin (mTOR), protein kinase B (AKT), Src, folate receptor alpha, and insulin-like growth factor-1 receptor (IGF-1R) pathways are in earlier phases of development for ovarian cancer. Attempts to target the epidermal growth factor receptor (EGFR) of ovarian tumors have been met with limited success; however, newer agents that inhibit this pathway show promise. Finally, with recognition of the role of Wee-1 in p53-deficient tumors, an inhibitor of this tyrosine kinase is being evaluated in recurrent ovarian cancer. The logistical challenge is to determine the optimal timing and proper combinations of novel agents independently as well as concomitantly with conventional chemotherapeutics. Reported results have been modest; however, our growing understanding of these pathways will be potentially reflected in greater impact on response and survival.
Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA. swestin@mdanderson.org
Shannon N
SN
Westin
Thomas J
TJ
Herzog
Robert L
RL
Coleman
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004260:DNA Repair / Q000187:drug effects; D015507:Drugs, Investigational / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases