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SearchShaun Stauffer, PhD, and Nima Sharifi, MD, discuss the roles of several proteins in castration resistant prostate cancer and their identification as novel targets for new therapeutics. The webinar session covers the development of these new drug candidates and how they might be applied to improve patient care.
Pioneering Prostate Cancer Research
Cleveland Clinic Innovations recently hosted a webinar that discussed the potential for new therapeutics to treat castration resistant prostate cancer during the first installment of the Innovation in Action: Revolutionizing Healthcare series.
Dr. Sharifi, formerly at Cleveland Clinic and now Scientific Director, Desai Sethi Urology Institute, University of Miami, elucidated the mechanisms of prostate cancer and the limitations of standard of care – namely patient resistance to hormonal therapy. He identified the enzyme 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) that enables tumors to persistently produce androgens and contributes to resistance. For patients inheriting an overactive variant of this enzyme, the survival rate decreases markedly. 3βHSD1’s central role in driving pathways that advance castration resistant prostate cancer makes it a prime target for new therapeutic interventions.
Similarly, Dr. Sharifi shared that his research had identified the protein hexose-6-phosphate dehydrogenase (H6PD) as complicit in contributing to hormonal resistance. Studies indicated that H6PD is upregulated in prostate cancer patients having undergone treatment with hormonal therapy and that blocking H6PD normalizes tumor metabolism and restores responsiveness to treatment. These data suggest targeting new alternative pathways for hormonal therapy resistance – an approach carrying immense therapeutic potential.
Cleveland Clinic Innovates Through Small Molecule Drug Development
Dr. Stauffer discussed his role as the Director of Cleveland Clinic’s Center for Therapeutics Discovery (C3TD). This medicinal chemistry laboratory was established with the mission to translate basic science discoveries made by Cleveland Clinic researchers into new small molecule therapeutics. He outlined the Center’s methodical process continuum– from initial target identification and library screening through rigorous optimization and testing stages and on to in vitro and in vivo preclinical models.
Dr. Stauffer and Dr. Sharifi discussed their collaboration in translating Dr. Sharifi’s work with 3βHSD1 and H6PD, respectively, into novel small molecule inhibitor drug candidates that have the hope of extending patients' life expectancy and improving their quality of life. They highlighted the vital role of multidisciplinary collaboration in driving progress in developing new treatments.
Navigating the complexity of drug discovery necessitates the utilization of differing approaches. Dr. Stauffer and Dr. Sharifi emphasized the persistence and creativity required to generate a drug development candidate that requires many years of preclinical and clinical testing.
The Journey Towards Clinical Trials and Collaborations
As such cutting-edge research inevitably demands substantial funding, the team noted the roles of foundations and industry partners. While the initial stages were backed by in-house resources, as the project scales and turns more resource-intensive, the need for partnerships to progress compounds from preclinical experiments into human trials becomes critical.
Looking ahead, Drs Stauffer and Sharifi predict that the new inhibitors' role would likely be alongside standard therapies, subject to clinical testing and treatment alternatives. Future work will identify patient cohorts that stand to benefit most from these treatments. Questions on the inhibitors' efficacy against other mechanisms of resistance, such as androgen receptor splice variant-7 (AR-V7), were addressed with cautious optimism.
Continuous Progress and Change
As drug development unfolds, it necessitates frequent adjustments and evolution in the progression plan. The team discussed the vital role of creating new assays, setting higher criteria as the project proceeds, and making use of counter screens for mitigating potential side effects or interaction with other targets. Looking into the future, the Center for Therapeutic Discovery will continue their exploration into other diseases like rare sarcoma, Alzheimer's disease, infectious disease, and cardiovascular diseases.
In conclusion, the speakers hailed the tremendous potential of these candidate therapeutics, expressing hope that their research will improve patient outcomes and transform the standard of care for prostate cancer and beyond. They encouraged continuous collaboration and feedback from the greater scientific and medical community.
Visit Cleveland Clinic’s Center for Therapeutics Discovery for any unanswered questions or further detailed insights into their upcoming projects. Stay tuned for exciting new sessions in this enlightening webinar series!
Pushing the boundaries of prostate cancer research, Cleveland Clinic’s Center for Therapeutics Discovery continues its journey to improving the quality of life for patients. Here's to the power of science and collaboration, bringing hope to the future of improved patient care.
View the full webinar “Small Molecule Therapeutics for Castration Resistant Prostate Cancer”.
