SU2C Scientific Research Teams
SU2C-PCF2 Dream Team: Targeting Adaptive Pathways in Metastatic Treatment-Resistant Prostate Cancer
Eric J. Small, M.D.
Professor of Medicine and Urology; Chief, Division of Hematology/Oncology, University Of California, San Francisco; Deputy Director, UCSF Helen Diller Family Comprehensive Cancer Center
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Owen N. Witte, M.D.
Investigator, Howard Hughes Medical Institute; Distinguished Professor, Microbiology, Immunology and Molecular Genetics; Director of the Broad Stem Cell Research, University of California, Los Angeles
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“We are incredibly excited about this project. 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 project will help identify the causes of resistance in an individual patient, and help us tailor therapy for that patient.”
- Team Leader Eric J. Small, M.D.
Prostate cancer is the most common nonskin cancer in America, and the second leading cause of death in U.S. men after lung cancer. Prostate cancer affects 1 in 6 men, with a new case estimated to occur every 2.1 minutes. Metastatic prostate cancer refers to cancerous tumors that have spread to other parts of the body, such as the bones.
One avenue for treatment of patients diagnosed with prostate cancer which has spread beyond the prostate is the reduction of the male hormone, testosterone. However, as with most hormone-dependent tumors, prostate cancer becomes refractory to hormone-deprivative therapy. These are referred to as treatment-resistant prostate cancer (TRPC).
The Stand Up To Cancer Dream Team led by Small and Witte will explore the idea that resistance to hormonal therapy occurs as a result of the prostate cancer cells using common cellular responses — what the Dream Team calls “adaptive pathways” — to escape the current prostate cancer therapies. They believe that, by identifying these pathways and inhibiting them, they will be able to overcome treatment resistance and profoundly improve the care of men affected by this fatal disease.
To test their idea, Small and Witte, along with a team composed of some of the best prostate cancer researchers on the West coast, have devised a three-pronged approach they termed “ACCESS, ASSESS and ACT.” They will systematically collect patient biopsies as well as blood samples (“access”), subject these to a comprehensive molecular assessment and pathway-based analysis to determine the activity level of known and novel pathways (“assess”), and will develop treatment approaches for individual patients based on these findings (“act”).
The Dream Team also proposes to centralize and integrate the considerable amount of data generated in the course of their work into a new online platform called 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 help the Dream Team’s Clinical Working Group recruit specific patients to specific trials.
Once the pathways activated in resistant metastatic tumors are identified, the Dream Team will devise co-targeting approaches that they will first validate in the laboratory before undertaking molecularly-guided clinical trials that will test novel combinations of therapeutics 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 the outcome for men with advanced prostate cancer.