An international team of investigators from centers in the United States and the United Kingdom, including Weill Cornell Medical College, have been awarded a grant for $10 million over a three-year period to study the molecular underpinnings of metastatic prostate cancer while creating a comprehensive testing system to optimize personalized treatments. The award was announced Sunday, April 1, during a press conference at the American Association for Cancer Research (AACR) 2012 Annual Meeting, held in Chicago from March 31 through April 4, 2012.
The grant, given by Stand Up To Cancer (SU2C) and the Prostate Cancer Foundation (PCF), along with the AACR, SU2C's scientific partner, will support basic research to both better understand and identify the mutations that drive the development of advanced prostate cancer - specifically, castration-resistant prostate cancer (CRPC) - and the establishment of a clinical trial and testing infrastructure aimed at creating an enhanced personalized medicine approach to treating the disease. Specialists will be able to analyze individual patient tumors, and conduct clinical trials testing various drugs and drug combinations against metastatic prostate cancer. Prostate cancer is considered castration-resistant when tumor growth continues, despite the use of hormonal therapies that lower cell growth-promoting androgen (testosterone) levels.
"Understanding the mutational landscape of individual tumors will allow us to better manage metastatic prostate cancers like castration-resistant prostate cancer," explains Dr. Mark A. Rubin, the project's principal investigator at Weill Cornell Medical College. The overarching goal of the grant is to eventually "position CRPC as a manageable and treatable disease with personalized medicine."
"It's a very exciting time because of the many recently developed treatments for advanced prostate cancer," says Dr. Rubin, the Homer T. Hirst Professor of Oncology in Pathology and vice chair for experimental pathology at Weill Cornell Medical College. "However, we recognize that none of these treatments are cures. For many of these patients, therapies will eventually stop working, and the focus of new research needs to be on the reasons treatments fail, and in developing new and improved therapies that are specific for each patient's cancer. This grant will enable us to set up a system by which we can analyze tumor biology and rationally plan treatment strategies for patients."
The grant, titled the SU2C-PCF Prostate Dream Team Translational Cancer Research Grant, supports the work of a prostate cancer "dream team." Led by Arul Chinnaiyan at the University of Michigan and Charles Sawyers at Memorial Sloan-Kettering Cancer Center, the team includes Weill Cornell Medical College, Dana-Farber Cancer Institute in Boston, Fred Hutchinson Cancer Center in Seattle, the Broad Institute in Cambridge, Mass., and the Royal Marsden Hospital in London.
The researchers plan to establish an infrastructure among these five participating medical centers, and two sequencing and computational analysis centers. They will enroll 500 patients with metastatic castration-resistant prostate cancer in clinical trials at five sites, and molecularly analyze biopsies of patient tumors in real-time, using this data to determine the most appropriate therapy for each patient. At the same time, such information may also be used to recommend clinical trials for patients, and may assist researchers in determining the reasons why treatments become ineffective in some individuals.
Dr. Rubin notes that the project not only seeks to demonstrate that such a centralized system is feasible for a single institution, but that it can be done across many institutions in a clinical trial setting. "Eventually, trials could use protocols developed in this project to facilitate how cancer is treated," he says.
One of the project's goals is to try to understand why therapies can become ineffective, despite working initially, and if patients may be treated with other types of therapies or participate in clinical trials, Dr. Rubin says. The researchers plan to develop cell line models to study tumor mutations to determine, for example, if they are the culprit behind such cancer recurrences in patients. In addition, the investigators plan to study novel combinations of drugs in clinical trials, including exploring the use of PARP inhibitors and drugs that inhibit the PTEN pathway, which is involved in cell signaling and growth. PTEN is a well known tumor suppressor gene. PARP inhibitors prevent an enzyme involved in DNA repair, especially in the repair of tumor cells, from working.
Another goal is to help train the next generation of investigators. To that end, Hamisha Beltran, a medical oncologist at Weill Cornell Medical College and a Prostate Cancer Foundation Young Investigator, will work closely with oncologists at other member institutions to conduct clinical trials. The Weill Cornell Medical College investigators will leverage their expertise in sequencing genetic information to search for early molecular changes in tumors that may be responsible for the development of aggressive prostate cancer.
"This project will provide us with information we've never seen before," Dr. Rubin says.
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