The path to personalized medicine in women's cancers: challenges and recent advances.

EDITORIAL URRENT C O PINION The path to personalized medicine in women’s cancers: challenges and recent advances Gottfried E. Konecny We are now two decades into the revolution of molecular biology in medicine, and it has been a little over 10 years since the human genome was cloned [1,2]. These advances have led to fundamen- tal changes in our understanding of cancer biology and tumor heterogeneity, resulting in clinically meaningful advances for patients diagnosed with breast and gynecologic cancers [3]. Moreover, tech- nical advances in the field of robotics, computer imaging, sentinel biopsies, and fertility preservation have further allowed us to tailor surgical treatments to the exact needs of an individual patient bringing us closer to the goal of truly personalized medicine. Although targeted therapy agents are increasingly available for breast and gynecologic cancers, many of the new promising drugs have produced disap- pointing results when tested in clinical trials, indi- cating that there are many challenges that must be addressed to advance this field. Progress is not as rapid as we would like. In this issue of Current Opinion in Obstetrics and Gynecology a series of articles highlight recent advances but also key challenges in our pursuit for personalized medicine in breast and gynecologic oncology. Progress in the understanding of the molecular events in ovarian cancer has prompted the need for a revised International Federation of Gynecology and Obstetrics staging system that may provide more accurate prognostic information and more specific guidance on personalized management of ovarian cancer than the older staging system that was last revised in 1988. In this issue, Kandukuri and Rao [4] eloquently highlight the newly revised Inter- national Federation of Gynecology and Obstetrics 2013 staging system for ovarian cancer and exactly pinpoint how it better embraces our current and improved understanding of the overlap of histologi- cal features and molecular characteristics of ovarian, tubal and peritoneal cancers. This new staging sys- tem will allow a more accurate characterization of these tumors and their clinical behavior and could facilitate the development of new personalized treatments in the near future. The rapidly increasing number of targeted thera- pies also provides a unique opportunity to improve treatment options for known rare gynecologic malignancies. However, their low frequency makes it difficult to test these new agents in randomized clinical trials. Ray-Coquard et al. [5] highlight in their article the need for international harmoniza- tion of medical practices and novel trial designs to speed up the clinical implementation of new treat- ments for known rare gynecologic tumors and the evolving rare molecular subtypes. The developing fragmentation of traditional disease entities into molecular subtypes is best described for breast cancer. It is well recognized that breast cancer is now a heterogeneous entity that is composed of several clinically and molecularly dis- tinct subtypes. About 10–15% of patients who are diagnosed with breast cancer are confronted with the diagnosis of triple-negative breast cancer (TNBC) defined by a lack of hormone receptor expression as well as lack of overexpression/amplification of HER2. Moreover, TNBC presents as a clinically and biologically heterogeneous entity itself and the low frequency of the resulting molecular sub- types makes it again very difficult to test new agents in randomized clinical trials. Despite these chal- lenges, however, progress is being made and Liedtke and Rody [6] update us on new treatment strategies for TNBC including the optimization of chemother- apy or identification of novel therapeutic targets but also discovery of biomarkers that show promise for predicting response to therapy. A key aspect to improving the efficacy of tailored treatments is understanding the mechanisms of drug resistance. For example, clinical benefits of antivascular endothelial growth factor therapy have been observed in ovarian cancer treatment trials; however, this use yielded only modest improvement Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA Correspondence to Gottfried E. Konecny, MD, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, 100 Medical Plaza, Suite 550, Los Angeles, CA 90025, USA. E-mail: gkonecny@mednet.ucla.edu Curr Opin Obstet Gynecol 2015, 27:45–47 DOI:10.1097/GCO.0000000000000149 1040-872X Copyright s 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-obgyn.com Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.