$1m grant to support genomic study of prostate cancer progression

Tuesday, August 4, 2015
Photo of Dr. Mark RubinDr. Mark Rubin Despite significant progress made in characterizing the "genomic landscapes" of primary prostate cancer and metastatic castrate resistant prostate cancer (mCRPC), studies have not yet been performed to identify the molecular alterations that mediate progression from primary cancer to mCRPC in patients.

Thanks to a $1 million grant from the Movember Foundation and Prostate Cancer Foundation (PCF), a team led by Mark Rubin, M.D., will attempt to identify these alterations, by analyzing matched primary tumor and mCRPC specimens. If successful, this project will identify molecular mediators and molecular pathways of prostate cancer progression that may serve as therapeutic targets and/or biomarkers that inform optimal therapies for individual patients.

"Cancer is a disease driven by the continued acquisition of genomic alterations that allow tumor cells to grow and divide abnormally, metastasize to other tissues, and develop resistance to therapies. Understanding the genomic alterations that confer each of these properties is critical for understanding disease evolution and designing optimal therapeutic strategies," Rubin said. 

Dr. Rubin and team are collecting archived primary prostate tumor samples from patients whose mCRPC tumor genomic and transcriptomic alterations have previously been characterized by the PCF-International Dream Team. Of the 500 patients assessed by the Dream Team, approximately 200 have primary tumor tissue available for this study.

The genomes and transcriptomes of these ~200 primary tumor samples will be sequenced and compared with alterations in matched metastatic tumors from the same patient in order to identify molecular alterations that mediate drug resistance and progression to mCRPC in individual patients.

Because of the continual acquisition of genomic mutations, tumors are heterogeneous and can be "multi-focal." This results in multiple tumor clones with different disease potentials that arise independently. Multiple regions of the primary tumor will be analyzed by these methods in order to identify the tumor clone that ultimately results in mCRPC.

Other investigators on the Integrative Genomics of Prostate Cancer Progression project include Joanna Cytra, M.D., also of Weill Cornell Medical College, as well as Scott Tomlins, M.D., Ph.D. of the University of Michigan and Ronglai Shen, Ph.D., of Memorial Sloan Kettering Cancer Center.

The grant was one of six Movember Foundation-PCF Challenge Awards funded by nearly $7 million made possible by the 2014 Movember U.S. Campaign. The awards are multi-year team science projects that focus specifically on permanent solutions for lasting remissions that advanced prostate cancer patients urgently need. To date, the Movember Foundation has contributed approximately $39 million, funding 28 projects globally, to help PCF further this aim.

"Our focus on metastatic prostate cancer fills a critical gap in our understanding of the disease," said Jonathan W. Simons, president and chief executive officer, PCF. "While our research efforts have helped to reduce the prostate cancer death rate by more than 50 percent, this advanced form of the disease remains the leading cause of prostate cancer deaths in the United States. Our vital partnership with the Movember Foundation brings us closer to conquering this disease."