The Prostate Cancer Foundation (PCF) has a legacy of not only funding the most impactful research in prostate cancer, but also creating new infrastructures, global knowledge networks, and research initiatives that support and accelerate prostate cancer research towards better treatment for advanced prostate cancer patients. For the past four years, PCF has hosted the Coffey-Holden Prostate Cancer Academy Meeting (CHPCA), as one of these important efforts. This unique 3-day meeting gathers approximately 75 investigators from prostate cancer and other research areas to brainstorm solutions for a critical unmet need in prostate cancer. This year’s meeting was held from June 23-26, 2016 in Coronado, California, and was themed “Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer.”
The CHPCA Meeting is modeled after the National Cancer Institute (NCI) Prouts Neck Meetings on Prostate Cancer, which were held from 1985-2007. The Prouts Neck Meetings were instrumental in driving new innovative studies and solutions for prostate cancer patients. Sorely missed by the prostate cancer community after being disbanded in 2007, the meeting was reactivated by PCF in 2013. In 2014, PCF renamed the meeting in honor of two great prostate cancer scientists and mentors who have made incalculable contributions to the field, Dr. Donald Coffey of Johns Hopkins University, and Dr. Stuart Holden, now of UCLA.
During a typical scientific conference, presentations are between 15-60 minutes, with very little time (sometimes none at all) allotted for questions and discussion. This format is not conducive to attendee interaction or intended to expose or solve critical unmet and under-addressed issues, but serves more to review science. The CHPCA Meeting format is a unique think-tank format where brief presentations (typically 10 minutes) are followed by lengthy discussion times to enable collective brainstorming on critical problems and paths for solutions. Another unique concept of these meetings, is that half of the attendees are early career PhD, MD, and MD/PhD scientists. This meeting provides opportunities for this next generation of leaders to interact with and form relationships with senior investigators.
The 2016 CHPCA Meeting focused on the topic of metastatic prostate cancer. Many critical topics were addressed with the goal of expanding our understanding of the biology of the disease and fast forwarding new treatment strategies. Several of the topics most relevant to patients are discussed below.
Accelerating precision medicine for metastatic prostate cancer patients
The goal of precision medicine is to match patients with therapies that target mutations unique to their tumors. Recent PCF-funded efforts have defined the landscape of mutations that occur in metastatic prostate tumors. In approximately 90% of the tumors studied, “actionable” mutations were identified — mutations that affect molecular pathways which are targetable by approved or experimental therapies. However, to go from “actionable,” to action, the efficacy of drugs targeting these mutations must be proven in clinical trials. As an example, PCF-researchers have shown that mutations in genes with roles in repairing damaged DNA sensitize prostate tumors to treatment with PARP-inhibitors. On a more comprehensive scale, a precision medicine basket trial was proposed by PCF-funded investigators and discussed in depth at the CHPCA Meeting. This “CATCH” (Castration resistant prostate cancer molecular Analysis for Therapy CHoice) trial proposes to sequence metastases from prostate cancer patients and then assign patients to receive one of ~16 targeted experimental therapies matched to their unique tumor mutations. Further planning, along with funding and support from pharmaceutical companies is being sought before the trial can begin, which is anticipated in 2017.
Studying exceptional responders
“Exceptional responders” are patients who exhibited a response lasting at least 6 months to a therapy that typically less than 10% of patients are predicted to respond to. A session at the CHPCA Meeting was dedicated to discussing how studies on exceptional responders can generate insights into how these therapies work and how efficacy may be enhanced for a broader set of patients. An underutilized NCI Exceptional Responders Initiative that performs extensive molecular and genomic analyses on tumors from exceptional responders was highlighted as a resource for collectively studying these patients. Clinicians were urged to participate by submitting tumor samples from their exceptional responder patients. The study of “exceptional non-responders” — patients who rapidly progress on multiple therapies — was also discussed as a strategy for gaining further insight into the mechanisms of therapeutic resistance. Because of the rarity of patients exhibiting exceptional responses and non-responses, collaborative efforts such as those being led by the NCI, are necessary to forward this area of study.
Bringing precision immunotherapy to patients with prostate cancer
Checkpoint immunotherapies including ipilimumab (Yervoy®), pembrolizumab (Keytruda®) and nivolumab (Opdivo®), act by reawakening tumor-killing immune cells that developed naturally or were elicited by tumor vaccines, but have been turned off by tumors. These therapies have cured a subset of patients with various tumor types including melanoma, but have not demonstrated much efficacy in prostate cancer to date. A few prostate cancer exceptional responders to checkpoint immunotherapies have recently been documented. Notably, tumors from many of these patients display a hyper-mutated genome due to defects in genes that protect the integrity of DNA. Mutated genes appear foreign to the immune system, as if a viral infection had taken place, and activates immune cells to target and kill any cell expressing that “foreign” protein. Thus, tumors with more mutations are more likely to have suppressed anti-tumor immune responses, which can be reactivated by checkpoint immunotherapies. A proposition was made at the CHPCA Meeting to start a scientific working group to discuss these cases, so that these promising therapies can be utilized for more prostate cancer patients. Precision immunotherapy clinical trials are also being initiated for patients whose tumors have mutations in genes that repair damaged DNA.
Other topics discussed at the meeting included understanding the biology of metastatic disease, therapeutically targeting non-tumor cells present in tumor metastases, developing predictive biomarkers and novel imaging technologies for earlier detection and better characterization of metastatic disease, and determining whether the gut flora (microbiome) affects prostate cancer development or treatment responses.
The 2017 CHPCA Meeting will be themed “Beyond the Androgen Receptor II: New Approaches to Understanding and Treating Metastatic Prostate Cancer.”
