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NEWS | October 9, 2012

UC Davis part of Stand Up To Cancer and Prostate Cancer Foundation research dream team

Up to $10 million grant over three years will fund leading-edge, collaborative research to develop personalized treatments for advanced prostate cancer

(PHILADELPHIA, Penn.)

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 second Dream Team project dedicated to prostate cancer research -- "Targeting Adaptive Pathways in Metastatic Treatment-Resistant Prostate Cancer."

Hsing-Jien Kung © UC Regents Hsing-Jien Kung © UC Regents

Among the six principal investigators on the $10 million grant is Hsing-Jien Kung, UC Davis distinguished professor of biochemistry and molecular medicine and associate director of basic science at the UC Davis Comprehensive Cancer Center.

"This puts UC Davis on the map of elite prostate cancer research teams in the nation," said Kung. "It provides an exciting opportunity to join the great, multidisciplinary talent pool to tackle the critical issue facing prostate cancer therapy -- the drug resistance."

The SU2C-PCF Prostate Dream Team Translational Cancer Research Grant will be led by Eric J. Small, 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, investigator of the Howard Hughes Medical Institute and distinguished professor of microbiology, immunology and molecular genetics at the University of California, Los Angeles (UCLA).

"We are incredibly excited about this project," said Small, who is also deputy director and director of clinical sciences in the UCSF Helen Diller Family Comprehensive Cancer Center. "Despite an unprecedented increase in the number of drugs that have been approved for the treatment of advanced prostate cancer, our patients still develop resistance to these agents, and still die from progressive disease. This SU2C-PCF project will help identify the causes of resistance in an individual patient, and help us tailor therapy for that patient."

The Dream Team scientists represent six world-class institutions: four campuses of the University of California (San Francisco, Los Angeles, Santa Cruz and Davis), Oregon Health & Science University in Portland, Ore., 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 special emphasis on metastatic disease and delivering near-term patient benefit.

"This grant is unique in its scope," said Dream Team co-leader Witte, who is also the director of the Broad Stem Cell Research Center at UCLA. "Two major funders and six different universities are combining their efforts in the spirit of collaborative science to attack this problem on a large scale."

Prostate cancer is the second most common cause of cancer death for men in the United States. According to PCF, one man dies every 18 minutes from this disease and a new case occurs every 2.1 minutes. 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."

"With generous support from Movember, PCF and its donors are pleased to team with Stand Up To Cancer to launch this unprecedented partnership for men with metastatic prostate cancer, whose cancers are resistant even to the newest treatments," commented Jonathan Simons, M.D., president and CEO 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."

The Prostate Dream Team Translational Cancer Research Project

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.

The 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.

Chris Evan © UC Regents
Christopher Evans

To test their idea, the researchers 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.

"The objectives of the Dream Team align very well with our UC Davis strengths in prostate cancer translational science," said Christopher P. Evans, professor and chairman of the UC Davis Department of Urology and one of the Dream Team researchers. "We will focus on acquisition of tumor tissue from patients undergoing therapies, grow these tumors in special mouse models and study mechanisms of resistance to those treatments. Ultimately it will be an opportunity to provide personalized therapy to patients."

Once the pathways activated in TRPC tumors are identified, the Dream Team will devise co-targeting approaches they validate in vivo using robust preclinical assessments. After validation they will implement molecularly guided clinical trials to 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 unique, 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, 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, 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, executive vice president and chief science officer of the PCF in Santa Monica, Calif. The JSAC is 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.

Dream Team principals and advocate members

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. Besides Small, Witte and Kung, team members are:

Principals:
•  Tomasz Beer, Oregon Health and Science University, Portland, Oreg.;
•  Martin Gleave, University of British Columbia, Vancouver, Canada;
•  Joshua Stuart, University of California, Santa Cruz, Calif.

Advocates:
•  Arthur Kern, University of California, San Francisco, Calif.; and
•  Roy Doumani, University of California, Los Angeles, Calif.

This Dream Team also includes five current or past Prostate Cancer Foundation Young Investigators and two PCF Therapy Consortium leaders, further strengthening a rapid bench-to-clinic precision oncology trial mechanism.

Prior to today's announcement, Stand Up To Cancer has awarded grants to seven Dream Teams, and 26 Innovative Research Grants have been awarded to individual young investigators. These recipients comprise more than 350 scientists from more than 65 institutions.

Last April, during the AACR Annual Meeting 2012, SU2C and PCF announced their first Prostate Cancer Dream Team project, titled "Precision Therapy for Advanced Prostate Cancer." Led by Arul M. Chinnaiyan, of the University of Michigan, and Charles L. Sawyers, of Memorial Sloan-Kettering Cancer Center, team members are drawn from five leading prostate cancer clinical research centers in Ann Arbor, New York, Boston, Seattle and London. These 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 information about the genetic makeup of these treatment-resistant prostate cancer patients, the 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 be working together to maximize synergy between their research projects.

About Stand Up To Cancer
Stand Up To Cancer (SU2C) -- a program of the Entertainment Industry Foundation (EIF), a 501(c)3 charitable organization -- raises funds to hasten the pace of groundbreaking translational research that can get new therapies to patients quickly and save lives. In the fall of 2007, a group of women whose lives have all been affected by cancer in profound ways began working together to marshal the resources of the media and entertainment industries in the fight against this disease.

Members of the SU2C Executive Leadership Council (ELC) include Talk Show Host, Journalist and well-known Cancer Advocate Katie Couric; Sherry Lansing, Chairperson of the Entertainment Industry Foundation's Board of Directors and founder of the Sherry Lansing Foundation; EIF President and CEO Lisa Paulsen; EIF Senior Vice President Kathleen Lobb; Rusty Robertson and Sue Schwartz of the Robertson Schwartz Agency; Pamela Oas Williams, President of Laura Ziskin Productions and Executive Producer of Stand Up To Cancer's In-House Production Team, and Nonprofit Executive Ellen Ziffren. All of the ELC members were co-producers of the 2012 televised special. The late Laura Ziskin, executive producer of both the Sept. 5, 2008 and Sept. 10, 2010 broadcasts, was also a member of the ELC. SU2C was formally launched on May 27, 2008. Sung Poblete, has served as SU2C's president and CEO since 2011.

SU2C's "Dream Team" approach to funding translational cancer research enables scientists from different disciplines at research centers across the country and internationally to collaborate on projects geared toward getting new, less toxic treatments to patients as quickly as possible. Monies also support innovative cancer research projects that are often deemed "too risky" by conventional funding sources. Sixty-five institutions are currently involved. As SU2C's scientific collaborator, the American Association for Cancer Research, led by a prestigious SU2C Scientific Advisory Committee, provides scientific oversight, expert review of the research projects and grants administration. For more information, visit standup2cancer.org.

About the Prostate Cancer Foundation
The Prostate Cancer Foundation (PCF) is the world's leading philanthropic organization funding and accelerating research. Founded in 1993 by Michael Milken, PCF has raised more than $500 million and provided funding to over 1,600 research projects at nearly 200 institutions in 15 countries around the world. Since 2008, it has supported 100 Young Investigators in seven countries and launched 17 PCF team science Challenge Awards. PCF advocates for greater awareness of prostate cancer and more efficient investment of governmental research funds supporting transformational cancer research. Prostate Cancer Foundation efforts over 19 years  have helped produce a 20-fold increase in government funding for prostate cancer and fast-forward research on research on four new Food and Drug Administration (FDA) drugs for advanced prostate cancer in the past two years. More information about PCF can be found at pcf.org.

About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org.

About the UC Davis Comprehensive Cancer Center
UC Davis Comprehensive Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its specialists provide compassionate, comprehensive care for more than 9,000 adults and children every year, and access to more than 150 clinical trials at any given time. Its innovative research program engages more than 280 scientists at UC Davis, Lawrence Livermore National Laboratory and Jackson Laboratory (JAX West), whose scientific partnerships advance discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis collaborates with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer care. Its community-based outreach and education programs address disparities in cancer outcomes across diverse populations. For more information, visit cancer.ucdavis.edu