Investigating the Link Between Metabolism and Prostate Cancer
Summary
- Speakers from the nation’s top academic centers shared research looking at how human metabolism impacts disease, including prostate cancer treatment and survival, at the third annual Miami Symposium on Human Metabolism.
- This year’s event focused more on metabolism and prostate cancer than previous years, featuring talks about ketogenic fasting, fatty acid inhibition interventions and the metabolic effects of prostate cancer therapies in patients.
- The Miller School of Medicine’s Dr. Nima Sharifi presented on how androgen deprivation therapy can drive prostate cancer therapy resistance.
At first glance, the Miami Symposium on Human Metabolism’s agenda doesn’t feature what one would typically see at oncology meetings nor does it fit a traditional metabolism meeting format.
While there were only 11 speakers, the quality of the roster of speakers rivaled that of medicine’s most attended conferences. Speakers from Massachusetts Institute of Technology (MIT), Memorial Sloan Kettering, Johns Hopkins, Weill Cornell, Harvard University, Cleveland Clinic and the University of Miami Miller School of Medicine presented during the session and the meeting ended with a highly engaging poster session that spurred more lively scientific discussions.
That’s intentional, said the meeting’s host, Nima Sharifi, M.D., Desai Sethi Urology Institute (DSUI) scientific director and a member of Sylvester Comprehensive Cancer Center, part of the Miller School.
The idea of the one-day meeting, he said, is to concentrate on the growing niche of health and disease research focused on metabolism in an intimate and collaborative setting.
“This year’s event focused more than past meetings on prostate cancer, where there is a lot of really exciting work related to human metabolism and prostate cancer treatment, as well as survivorship, including how metabolism might address side effects from various therapies,” Dr. Sharifi said. “Having said that, this meeting wasn’t only about prostate cancer. For example, Zoltan Pierre Arrany, M.D., Ph.D., co-director of the Institute for Diabetes, Obesity and Metabolism at the University of Pennsylvania, shared his work in interventional cardiac metabolic pathophysiology.”
Prostate Cancer’s Metabolic Vulnerabilities
Daniel Schmidt, M.D., Ph.D., a radiation oncologist at Beth Israel Deaconess Medical Center, has attended all three symposia.
“I keep coming back because I find it to be a unique opportunity to hear about current clinical trials and the latest scientific discoveries related to human metabolism in an intimate environment,” he said. “As a prostate cancer researcher and GU radiation oncologist, I find the talks to be highly relevant to my field. The Miami Symposium on Human Metabolism does a wonderful job of encouraging interactive podium and poster presentations that spawn new ideas and collaborations.”
Dr. Schmidt presented “Pyruvate Kinase is a Therapeutic Target in Prostate Cancer,” a talk centered on his team’s work to identify metabolic vulnerabilities of prostate cancer, specifically pertaining to how prostate cancer cells proliferate.
“We propose that by altering the activity of select glycolytic enzymes, we can starve cells of key metabolites required for proliferation,” he said. “In line with this, we find that drugs that increase the activity of pyruvate kinase, the enzyme that catalyzes the final reaction in glycolysis, have profound, antiproliferative effects in prostate cancer by lowering serine levels.”
This results in activation of the integrated stress response, followed by cell cycle arrest. These effects are most pronounced when cells are in a high-lactate environment. That’s the case for most tumors, but not normal tissues.
“We find that this happens because when lactate levels are high, GAPDH (glyceraldehyde 3-phosphate dehydrogenase) becomes rate limiting for glycolysis and activating pyruvate kinase under these conditions results in depletion of glycolytic intermediates required for serine synthesis,” Dr. Schmidt said. “These findings suggest that pyruvate kinase activators will have a favorable therapeutic index in the clinic because they will deplete serine in tumors, while having minimal effect on normal tissue metabolism.”
Metabolism’s Influence on Health and Disease
Metabolism is an impactful path for research on human health and disease, which could lead to the discovery of new drugs and influence the successful treatment and management of patients with cancer and other diseases, according to Dr. Sharifi. The Miller School professor of urology presented on how androgen deprivation therapy leaves residual androgens that can drive prostate cancer therapy resistance.
Speakers representing multiple specialties shared their findings in such areas as dietary interventions, ketones and fatty acid synthase inhibition in prostate cancer.
• Laura Sena, M.D., Ph.D., a prostate cancer oncologist at Johns Hopkins Medicine, presented “Ketogenic Fasting Interventions in Prostate Cancer.”
• Massimo Loda, M.D., chair of pathology at Cornell University, presented “Fatty Acid Synthase Inhibition Clinical Studies in Prostate Cancer.”
• Zhipeng Wang, Ph.D., DSUI assistant professor of urology and Sylvester member, shared his research on “Ketone-body Dependent Post Translational Modifications.”
• Yuanyuan Qiao, Ph.D., department of pathology at the University of Michigan, presented “A Stress-Adaptive Lipid Kinase Axis Defines Metabolic Vulnerabilities in Neuroendocrine Prostate Cancer.”
• Alicia Morgans, M.D., M.P.H., who leads cancer survivorship at Dana-Farber Cancer Institute, talked about treatment-related side effects in men with prostate cancer and how to manage them from an endocrine standpoint in “Metabolic Health and Prostate Cancer Survivorship.”
• Charles Ryan, M.D., a genitourinary medical oncologist at Memorial Sloan Kettering, addressed how prostate cancer metabolism can lead to resistance mechanisms in “Androgen Production, Uptake and Conversion Enzymes in CRPC.”
• Shaun Stauffer, Ph.D., a chemist from Cleveland Clinic and long-time collaborator with Dr. Sharifi on drug development, presented “Targeting Metabolism in Prostate Cancer.”
• Daniel Isom, Ph.D., associate professor of molecular and cellular pharmacology at the Miller School, presented on how mitochondria may be transported between cells and how “super dark proteins” may function in metabolism in “Dark GPCRs and Mitochondrial Transport.”
“The symposium not only offered a series of relevant and timely talks in metabolism and the human condition but also featured a poster session of abstracts by graduate students, clinical fellows and postdoctoral fellows,” Dr. Sharifi said. “We give some trainees travel awards, so they have opportunities to share their work and intermingle with established researchers in this specialized niche. The Miami Symposium on Human Metabolism is a place to be every year, regardless of the stage of one’s research career.”
Tags: Desai Sethi Urology Institute, Dr. Nima Sharifi, Miami Symposium on Human Metabolism, prostate cancer, Sylverster Comprehensive Cancer Center