An update on the Prostate Cancer Moon Shot's efforts to improve outcomes, save lives
Clayton R. Boldt, Ph.D.
Excluding skin cancers, prostate cancer is the most commonly diagnosed cancer among men in the United States. According to the American Cancer Society, more than 160,000 new cases will be diagnosed in the country this year, and more than 29,000 will die from the disease.
MD Anderson’s Prostate Cancer Moon Shot™ was founded to improve outcomes and save the lives of men diagnosed with prostate cancer. It’s a part of MD Anderson’s Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients’ lives.
Q: Why is there a need for a Moon Shot devoted to prostate cancer?
A: Despite significant research, prostate cancer remains the second leading cause of cancer death in U.S. men, behind only lung cancer. The remarkable increase in our understanding of prostate cancer from that research has yet to translate into proportional improvements in outcomes. We attribute this “application challenge” to the marked heterogeneity of the disease over time and difficulties in serially sampling relevant tissues. The Prostate Cancer Moon Shot plays a critical role in filling this gap by co-developing new treatment methods and therapeutic targets for rapid validation in the clinic.
Q: Immunotherapy has been successful recently in treating several cancer types, but prostate cancer has been challenging. Why has prostate cancer not seen the same success with immunotherapy to date as other cancers?
A:Though some patients achieve a striking benefit from immunotherapy, most do not. Therefore, prostate cancer overall must be included among the cancers that are not responsive to immunotherapy. We, and others, have attributed the resistance to the central role of a cancer-associated microenvironment that is “immunosuppressive” and emerging as a targetable mechanism of resistance.
Q: Can you describe your Moon Shot projects and how you’re working to overcome those challenges?
A: The Prostate Cancer Moon Shot is working to improve patient outcomes and address these challenges in several ways. First, we are developing a liquid biopsy method to clinically monitor cancer evolution, which will help inform clinicians regarding the application of specific therapies. Additionally, we are identifying markers to anticipate the emergence of bone metastases, and applying the markers to develop a “bone development pathway” in combination with immunotherapy.
Q: What results have you seen thus far, and how do you think this will advance the field in the coming years?
A: We demonstrated that some men with early prostate cancer will benefit from a sustained cancer control after recovery of testosterone, which will lead to more effective and less toxic therapy.
We also have demonstrated that the glucocorticoid receptor is a component of the “nuclear receptor hormone complex” implicated in initial resistance to androgen signaling.
Our research implicated fibroblast growth factor (FGF) signaling as a central pathway to prostate cancer progression in bone, and we are working to effectively target it clinically and co-clinically.
Finally, we have identified subsets of patients with prostate cancer that are both resistant and receptive to immunotherapy, which can help us better treat these men. Our findings have implicated myeloid-derived suppressor cells (MDSCs) and an immune-regulatory molecule, VISTA, with immunotherapy resistance.
Q: How has the Moon Shots Program enabled you to tackle these questions in ways you may not have been able to previously?
A: The Moon Shots Program has allowed us to access and develop critical enabling technologies in a way that was not previously possible. Further, it has supported the assembly of unmatched multi-disciplinary teams of clinical and laboratory researchers, who have transformed our approach to research through effective integration.