Tomasz Beer, M.D., deputy director of the Knight Cancer Institute at Oregon Health & Science University (OHSU), was selected as one of six top scientists to take part in a research Dream Team that joins together world-class institutions to study treatments for advanced prostate cancer. Funding for the project will be provided by a three-year grant for up to $10 million.
The research collaborative is one of only two prostate cancer Dream Teams that have been recruited and organized by Stand Up To Cancer (SU2C) and the Prostate Cancer Foundation (PCF) along with the American Association for Cancer Research (AACR), which is SU2C’s scientific partner.
“It is an honor to be part of a team of this caliber that is devoted to men who currently have no reliable treatment options,” Beer said. “There have been many important advances in prostate cancer treatment in the past few years, but we can do better. We need to know more about why some men don’t respond to these therapies and why others respond and then see their cancer become resistant. This knowledge will serve as the road map for the next generation of treatments.”
The Knight Cancer Institute is committed to making personalized cancer treatments a reality for all patients. The institute’s director, Brian Druker, M.D., proved it was possible to shut down the growth of cancer cells without harming healthy ones – a discovery that helped make once-fatal forms of the disease manageable and that ushered in a new generation of targeted cancer therapies.
“By collaborating and sharing what we’ve learned through projects such as this new Dream Team, we expect to accelerate the rate of progress,” added Beer, who recently co-authored the book, “Cancer Clinical Trials.”
Beer, Alumkal and Thomas are part of the OHSU Prostate Cancer Research Program that currently leads international Phase III clinical trials of the next generation hormonal therapy enzalutamide, the immunotherapy agent ipilimumab, and the targeted agent custirsen. Their group also studies prostate cancer in the laboratory to understand what drives these tumors and the indicators, or biomarkers, that provide clues about the disease, so that the next generation of drugs can be developed.
Prostate cancer is the second most common cause of cancer death for men in the United States. One man dies every 18 minutes from this disease and a new case occurs every 2.1 minutes, according to the Prostate Cancer Foundation. More than 2 million American men are living with prostate cancer and more than 16 million men are affected worldwide.
“The need for research on more effective ways to treat prostate cancer is truly urgent,” said Sherry Lansing, SU2C co-founder, chairperson of the Entertainment Industry Foundation’s (EIF) Board of Directors and founder of the Sherry Lansing Foundation. “We are excited to continue collaborating with the Prostate Cancer Foundation to address that need.”
The Dream Team’s research project, “Targeting Adaptive Pathways in Metastatic Treatment-Resistant Prostate Cancer,” will include scientists from six institutions. Along with the Knight Cancer Institute, the team will include researchers from four campuses of the University of California (San Francisco, Los Angeles, Santa Cruz and Davis) and the University of British Columbia in Vancouver, Canada. The team is organized around five working groups integrating expertise from each of the six centers. A sixth “knowledge-exchange” working group will coordinate and harmonize activities of the Dream Team, which will address therapeutic interventions for advanced prostate cancer with emphasis on metastatic disease and delivering near-term patient benefit.
The team will be led by Eric J. Small, M.D., professor of medicine and urology and chief of the division of hematology and oncology at the University of California, San Francisco (UCSF), and Owen N. Witte, M.D., investigator from the Howard Hughes Medical Institute and distinguished professor of microbiology, immunology and molecular genetics at the University of California, Los Angeles (UCLA).
Launching this prostate cancer Dream Team, represents an unprecedented partnership on behalf of men with metastatic prostate cancer, said Jonathan Simons, M.D., president and chief executive officer of the Prostate Cancer Foundation. “One potential transformational benefit of this project for prostate cancer patients will be a new application called MedBook, a social network for medical science that is being created by former Apple Vice President Ted Goldstein, who helped Apple create tools and operating systems for Macintosh and iPhones. The precision prostate oncology MedBook application will be similar to an iPad app, linking patients, doctors and researchers in a participatory information platform that will speed the matching of new medicines targeted at nine new druggable pathways to the patients who will benefit most.”
Understanding resistant tumors
Treatment of patients diagnosed with hormone-dependent prostate cancer includes chemical or surgical castration, using drugs or surgery to reduce androgen hormones such as testosterone and dihydrotestosterone. However, as with most hormone-dependent tumors, prostate cancer becomes resistant to this therapy. These resistant tumors are referred to as treatment-resistant prostate cancer or TRPC.
This new Stand Up To Cancer Dream Team will explore the idea that resistance is a result of the prostate cancer cells using common cellular responses, called adaptive pathways, to escape current therapies. The team believes that by identifying these pathways and inhibiting them, they will be able to overcome treatment resistance and profoundly improve survival and quality of life for these patients.
To test their idea, Small, Witte, Beer and their colleagues will systematically subject patient biopsies (fixed, frozen and fresh tissue) and blood samples to a comprehensive molecular assessment and pathway-based analysis to determine the activity level of known and novel pathways. Once the pathways activated in TRPC tumors are identified, the Dream Team will devise co-targeting approaches in the laboratory. After validation they will test novel therapeutic combinations that co-target adaptive pathways associated with resistance. By combining established therapies with new treatments that co-target adaptive pathways, the Dream Team hopes to dramatically improve outcomes for men with advanced prostate cancer.
The Dream Team also proposes to centralize and integrate the considerable amount of data generated by their work into MedBook, which will use a simple social media concept to support information exchange and discussion. The centralized information will be updated continuously based on new data, and contribute to the development of molecular disease models that codify the most current clinically actionable adaptive pathways in metastatic TRPC. This information will be instrumental to the Dream Team’s Clinical Working Group for recruiting patients to specific trials. The project is estimated to start later this fall, with the first clinical trials scheduled to open in 2013.
Dream Team selected through rigorous process
A SU2C-PCF Joint Scientific Advisory Committee (JSAC) conducted a unique, rapid and rigorous evaluation of the applications using a multistep 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 PCF in Santa Monica, Calif. The JSAC is also comprised of nine highly accomplished senior laboratory researchers and physician-scientists, as well as two advocates.
The review process began with a call for letters of intent by the American Association for Cancer Research in October 2011. The committee then chose four finalist teams, each of which met in person with the JSAC to present plans for their research and respond to questions about their projects — a level of interaction between applicants and reviewers that is unique among scientific review processes.
Combining young investigators and senior scientists
The “Targeting Adaptive Pathways in Metastatic Treatment-Resistant Prostate Cancer” Dream Team consists of a multidisciplinary 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. The other principals on the team besides, Small, Witte and Beer are: Martin Gleave, M.D., University of British Columbia, Vancouver, Canada; Hsing-Jien Kung, Ph.D., University of California, Davis, Calif.; and Joshua Stuart, Ph.D., University of California, Santa Cruz, Calif.
Prior to today’s announcement, Stand Up To Cancer has awarded grants to just seven Dream Teams. Joe W. Gray, Ph.D., one of the lead scientists with the Knight Cancer Institute, co-leads a breast cancer Dream Team focused on research that will lead to less toxic treatments for breast cancer.
The first Prostate Cancer Dream Team was assembled in April. This group of researchers will harness the power of so-called next-generation sequencing technology to decode 500 patients’ cancer genomes, the 3.1 billion bases of DNA sequence that constitute the entire set of genetic instructions found in a cell. Armed with the information about the genetic makeup of these treatment-resistant prostate cancer patients, this Dream Team expects to be able to direct patients toward the treatment most likely to have an effect on their tumors. It is anticipated that the two Prostate Cancer Dream Teams will work together to maximize synergy between their research projects.
Tomasz Beer, M.D., F.A.C.P., serves as the Grover C. Bagby Endowed Chair for Prostate Cancer Research; a professor of medicine in the Department of Hematology & Medical Oncology; and director of the Prostate Cancer Research Program at the Knight Cancer Institute at Oregon Health & Science University. Beer recently co-authored the book, “Cancer Clinical Trials,” and continues to share his insights on a blog by the same name.