Cancer genomics and clinical practice: how can we close the gap more quickly?

EDITORIAL URRENT C O PINION Cancer genomics and clinical practice: how can we close the gap more quickly? Gottfried E. Konecny During his State of the Union address on January 12, 2016, President Barack Obama announced the estab- lishment of a Cancer Moonshot to accelerate cancer research. The initiative – led by Vice President Joe Biden – aims to make more therapies available to more patients, while also improving our ability to prevent cancer and detect it at an early stage. A task force was charged with identifying key priorities some of which were accelerating our understanding of cancer and its prevention, early detection, treat- ment, and cure as well as encouraging the develop- ment of new cancer treatments. As of 2017, it is now fair to say that in oncology the concept of precision medicine, incorporating genomics into drug discov- ery and cancer treatment strategies, has finally been realized and is now firmly embedded in ongoing drug discovery programs and cancer treatments. This particularly holds true for diseases such as breast and nonsmall cell lung cancer or melanoma where multiple new-targeted therapies have been approved in the last decade. These new therapies refer to a new generation of cancer drugs that are designed to interfere with a specific molecular target that is believed to have a critical role in tumor growth or progression. This approach contrasts with the conventional, more empirical approach used to develop cytotoxic chemotherapeutics – the main- stay of cancer drug development in past decades. However, despite significant progress in the treat- ment of certain forms of cancer, it must be empha- sized that very little progress has been made in the identification of novel targeted therapies for women diagnosed with gynecologic malignancies – cyto- toxic chemotherapies are still the mainstay of treat- ment in 2017. Consistent with this absence of progress for patients diagnosed with gynecologic malignancies survival rates for patients diagnosed with ovarian, endometrial or cervical cancer have at large remained unchanged or have only minimally improved over the last 30 years [1,2]. Needless to say that during this time the importance of tumor surgery and platinum/taxane-based chemotherapy as treatment for ovarian, endometrial and cervical cancer has been recognized, but the small survival gains have been predominately realized through prolonging the life expectancy of women with recurrent ovarian cancer, not through an increased cure rate. This lack of progress in new drug development for women diagnosed with gynecologic malignan- cies is, however, astounding and in stark contrast to the recent revolution in our understanding of can- cer biology and tumor heterogeneity. Clearly, can- cer genomics stands as a critical foundation for novel pathway and drug discovery and given the limitations of current therapeutic standards for the treatment of gynecologic malignancies, there is lit- tle doubt that a better and quicker translation of cancer genomics into rational clinical trials could create real improvements for patients diagnosed with gynecologic cancers. In this issue of Current Opinion in Obstetrics and Gynecology a series of articles highlight recent advances but also key challenges in our pursuit to utilize cancer genomics for new drug discovery and personalized medicine in gynecologic oncology. Bayer et al. (pp. 4–11) illustrated the power of a concerted large integrative cancer genomics effort to identify novel genes and proteins in cancer. This article beautifully illustrates how genomics can transform the path to drug discovery. In the 1990s, short expressed gene sequences were gener- ated from cDNA libraries that were assembled from mRNA isolated from cells and tissues of interest. Full-length sequences were then overexpressed in transgenic mice and were subsequently screened for radiographical, biochemical, hematological, and histological differences from their wild-type litter- mates as a means of deciphering gene function. This effort led to the discovery of osteoprotegerin (OPG) Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA Correspondence to Dr Gottfried E. Konecny, MD, Department of Medi- cine, David Geffen School of Medicine, University of California, 100 Medical Plaza, Suite 550, Los Angeles, CA 90025, USA. E-mail: gko- necny@mednet.ucla.edu Curr Opin Obstet Gynecol 2017, 29:1–3 DOI:10.1097/GCO.0000000000000341 1040-872X Copyright s 2017 Wolters Kluwer Health, Inc. All rights reserved. www.co-obgyn.com Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.