Authors:
 Lotte Burgering, Shawn M. Davidson, Catherine Wu, Craig J. Thomas, Massimo Loda, Matthew G. Vander Heiden
 
 
 Affiliations:
 Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA; Harvard Medical School, Boston, MA; Koch Institute, Massachusetts Institute of Technology, Cambridge, MA; Dana Farber Cancer Institute, Boston, MA; Utrecht University, Utrecht, The Netherlands; Department of Pathology, Weill Cornell Medicine, New York, NY; Lewis-Sigler Institute, Princeton University, Princeton, NJ; National Center for Advancing Translational Sciences at NIH, Bethesda, MD
 
 
 Abstract Body:
 Pyruvate kinase M2 (PKM2) is the predominant isoform of pyruvate kinase expressed in most rapidly dividing cells, including cancer cells, and is important for regulating anabolic metabolism to support increased metabolic demand of actively proliferating cells. Drugs targeting PKM2 are currently being developed for use in patients. We have found that prostate cancer expresses PKM2 suggesting that PKM2-targeted therapy may be an effective treatment for prostate cancer. In support of this hypothesis, find that targeting PKM2 either genetically or pharmacologically in a mouse model of prostate cancer delays prostate cancer growth and improves survival. TEPP-46, a PKM2 activator, reduces serine synthesis and induces dependence on exogenous serine for de novo purine synthesis. Preliminarily, we find that pyruvate kinase activity and serine synthesis are linked by the NAD+/NADH ratio. Efforts are currently underway to determine how to best incorporate PKM2-targeted agents into prostate cancer management.
 
 
 Funding Acknowledgments:
 DF/HCC SPORE in Prostate Cancer (P50 CA090381-15); Harvard KL2/Catalyst Award (KL2 TR002542)
 
 
 Corresponding Author Email:
 dschmidt@bidmc.harvard.edu
 
 
 Conflict of Interest:
 Nothing to Disclose

Targeting Pyruvate Kinase to Induce Metabolic Dependencies in Prostate Cancer