Arul M. Chinnaiyan, M.D., Ph.D., of the University of Michigan Comprehensive Cancer Center will lead the Dream Team project titled Precision Therapy for Advanced Prostate Cancer
Written by Nicole Fawcett
CHICAGO - Stand Up To Cancer (SU2C) and the Prostate Cancer Foundation (PCF), along with the American Association for Cancer Research (AACR), SU2C's scientific partner, announced the formation of a new Dream Team dedicated to prostate cancer research.
Arul M. Chinnaiyan, M.D., Ph.D., of the University of Michigan Comprehensive Cancer Center, and Charles L. Sawyers, M.D., of Memorial Sloan-Kettering Cancer Center, will lead the Dream Team project titled "Precision Therapy for Advanced Prostate Cancer." The Dream Team scientists are drawn from five leading prostate cancer clinical research centers in Ann Arbor, New York, Boston, Seattle and London.
The SU2C-PCF Prostate Dream Team Translational Cancer Research Grant will provide funding of $10 million over a three-year period for a seven-center project including both clinical centers and two research infrastructure sites that will address therapeutic interventions for advanced prostate cancer, with special emphasis on metastatic disease, and deliver near-term patient benefit through investigation by a multidisciplinary, multi-institutional, synergistic Dream Team of expert investigators.
Prostate cancer is the second most common cause of death for men in the United States. According to PCF, one man dies every 18 minutes from this disease. In addition, a new case occurs every 2.4 minutes. More than 2 million American men are currently living with prostate cancer and more than 16 million men are affected worldwide.
"Through this unique partnership with PCF, we will focus critically needed research on advanced prostate cancer," said Sherry Lansing, one of SU2C's co-founders. "Our collective goal is to produce personalized treatment approaches that will begin to benefit patients in the next few years."
"We are excited to announce and fund this Dream Team in partnership with Stand Up To Cancer. Healthy competition for the prestigious research award brought out tremendous innovation - well beyond what the National Cancer Institute or Department of Defense is currently funding," commented Jonathan Simons, M.D., president and CEO of the Prostate Cancer Foundation. "We are highly confident that the cross-institutional teams of researchers led by Drs. Chinnaiyan and Sawyers will significantly fast-forward actionable therapeutic sciences for men with treatment- resistant metastatic prostate cancer."
Chinnaiyan is a clinical pathologist and investigator at the Howard Hughes Medical Institute, S.P. Hicks endowed professor of pathology and professor of urology at the University of Michigan Medical School, and an American Cancer Society research professor. He also serves as the inaugural director of the Michigan Center for Translational Pathology. The Chinnaiyan laboratory has focused on functional genomic, proteomic, metabolomic and bioinformatic approaches to study cancer for the purposes of understanding tumor biology, as well as to discover clinical biomarkers. Chinnaiyan has also been the recipient of PCF career-development funding and research awards since 2001.
Chinnaiyan's lab was the first to identify a gene fusion that occurs in half of all prostate cancers. This finding is the basis for the research that will be done as part of this new grant.
"Utilizing this Dream Team grant, we will be able to bring together great scientists and clinicians from around the world to join in the fight against metastatic prostate cancer. We hope this unique model of research will lead to patient benefit in the short term," said Chinnaiyan.
Sawyers is chair of the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center in New York, and a Howard Hughes Medical Institute investigator. Additionally, he is a professor in the cell and developmental biology program and the department of medicine at the Joan and Sanford Weill Graduate School of Medical Sciences of Cornell University, also in New York. Sawyers' PCF-funded research in prostate cancer molecular pharmacology defined upregulation of androgen receptor signaling as the primary mechanism of resistance to hormone therapy, resulting in the discovery of the antiandrogen MDV3100 that was recently shown to prolong survival in men with metastatic prostate cancer. Sawyers has been a recipient of PCF research award support since 1996.
"The unique research model facilitated by SU2C will allow unparalleled collaborations in the field of prostate cancer therapy research," said Sawyers. "We hope that our project will move the world of precision medicine forward for the benefit of those who suffer with the disease and those who care for them."
The Prostate Dream Team Translational Cancer Research Project
Prostate cancer, like other types of cancer, is not a homogeneous disease. For example, up to 50 percent of castration-resistant prostate cancer (CRPC) patients have a genetic aberration of two genes fused together. Often these fusions, which were first reported by Chinnaiyan's lab, involve the ETS genes, a group of oncogenes that play an important role in the progression of prostate cancer. A majority also have a "deletion" or loss of an entire gene called PTEN. The diversity of genetic aberrations found in prostate cancer suggests that treatment decisions will require a personalized or precision approach - matching treatment to specific characteristics of a tumor. The premise for this proposal is that information about the genetic makeup of an individual's CRPC may guide the doctor to choose a "personalized" treatment for that patient.
Chinnaiyan, Sawyers and the members of their Dream Team will focus on patients with metastatic prostate cancer. First, the team will implement a multi-institutional study that systematically evaluates the prostate cancer genomes of patients enrolling in four clinical trials, evaluating novel drugs for CRPC or beginning treatment with approved drugs like abiraterone.
They will identify predictors of why some patients respond to these therapies, as well as predictors of resistance to these therapies. The study will capture a molecular snapshot of a patient's cancer and incorporate this information into the clinical trials. It will also enable a framework that will facilitate progress toward a personalized approach for evaluating new drugs and treating patients with prostate cancer.
The delivery of clinically valuable information based on the analyses of each patient's tumor will improve the lives of patients with prostate cancer. While state-of-the-art technology in DNA sequencing has dramatically accelerated biomedical research, translation into a clinical setting has numerous barriers that limit the potential benefits. This multi-disciplinary, multi-institutional effort establishes a framework for translating research into precision prostate cancer medicine for patient care.
The project is estimated to start mid-2012 with the first clinical trials scheduled to open in early 2013.
Dream Team Selected Through Unique, Rigorous Process
A SU2C-PCF Joint Scientific Advisory Committee (JSAC) conducted a unique, rapid and rigorous evaluation of the applications via a multi-step scientific review process.
The committee is chaired by Nobel Laureate Phillip A. Sharp, Ph.D., institute professor at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology in Cambridge, Mass. It is co-chaired by SU2C representative William G. Nelson, M.D., Ph.D., the Marion I. Knott director and professor of oncology, and director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, Md., and PCF representative Howard R. Soule, Ph.D., executive vice president and chief science officer of the Prostate Cancer Foundation. The JSAC is comprised of highly accomplished senior laboratory researchers and physician-scientists, as well as advocates.
The review process began with a call for letters of intent by the AACR in October. The committee then chose four finalist teams, each of which met with the JSAC to present the plans for their research and respond to questions about their projects - a level of interaction between applicants and reviewers that are unique in a scientific review process.
Prostate Dream Team Principals and Advocate Members
The "Precision Therapy for Advanced Prostate Cancer" Dream Team consists of a multi-disciplinary group of experts that includes laboratory and clinical researchers, young investigators and senior scientists who have not worked together in the past, as well as patient advocates. In addition to Chinnaiyan and Sawyers, team members are:
- Philip W. Kantoff, M.D., Dana-Farber Cancer Institute, Boston, Mass.
- Levi A. Garraway, M.D., Ph.D., Broad Institute, Cambridge, Mass.
- Peter S. Nelson, M.D., Fred Hutchinson Cancer Research Center/University of Washington, Seattle, Wash.
- Johann S. de Bono, M.D., Institute for Cancer Research/Royal Marsden NHS Foundation Trust, London, U.K.
- Mark A. Rubin, M.D., Weill Medical College of Cornell University, New York, N.Y.
- Doug Pergament, University of Michigan, Ann Arbor, Mich.
- James Kiefert, Fred Hutchinson Cancer Research Center, Seattle, Wash.
- Stan Klein, Dana-Farber Cancer Institute, Boston, Mass.
- Thomas Farrington, Dana-Farber Cancer Institute/Broad Institute, Boston, Mass.
- Ian Liston, Institute for Cancer Research/Royal Marsden NHS Foundation Trust, London, U.K.
- Grant Gregory, Memorial Sloan-Kettering Cancer Center, New York, N.Y.
Prior to today's announcement, SU2C has awarded grants to six Dream Teams and 26 Innovative Research Grants have been awarded to young investigators. These recipients comprise 270 scientists from 67 unique institutions. U-M Comprehensive Cancer Center researchers are already part of one dream team and two scientists have received Innovative Research Grants.