Posted December 11, 2018

David Jarrard, M.D., University of Wisconsin
Vincent Cryns, M.D., University of Wisconsin

Progression to castrate-resistant prostate cancer (CRPC), the potentially lethal form of prostate cancer (PCa), can result after the initiation of androgen deprivation therapy (ADT). One underutilized therapeutic strategy that has the potential to dramatically improve outcomes is eradicating the persistent cancer cells that remain after ADT and likely play a key role in the development of CRPC. Data from the laboratories of Drs. David Jarrard and Vincent Cryns at the University of Wisconsin suggests that these resistant cancer cells adopt a senescent phenotype in which they stop growing but still survive and secrete substances to promote tumor growth. They discovered that these cells have certain characteristics that may make them susceptible to drugs that affect metabolism. As such, they predicted that metformin, which is a safe, low-cost drug with minimal side effects used to treat diabetes, would eliminate these metabolically active cancer cells remaining after ADT and improve cancer outcomes.

With funding from a FY15 Idea Development Award, Drs. Jarrard and Cryns and their laboratories are conducting experiments in cellular and animal models to determine the efficacy and mechanisms involved in combining metformin with ADT. They have also examined this combination therapy, in conjunction with co-investigator Dr. Kyle Richards, by using existing electronic health record data in a large national Veterans Affair database of men with PCa who were treated with ADT. Some of these men were also treated with metformin for diabetes or pre-diabetes and some were not. Through this, they found that men with PCa who were treated with both ADT and metformin had improved survival compared to men just receiving ADT. Metformin also reduced the risk of cancer spreading to the bone.

Definitive data in a clinical trial is required before this approach could be clinically used to treat PCa patients. Plans for such a trial are ongoing, which would further define exactly which patients were most likely to benefit from this approach. Because metformin is an inexpensive drug already FDA approved for diabetes treatment, it has the potential to move into the clinic quickly and help improve treatment outcomes for men with PCa undergoing ADT.

Publication:

Richards KA, Liou JI, Cryns VL, et al. 2018. Metformin Use Is Associated with Improved Survival in Patients with Advanced Prostate Cancer on Androgen Deprivation Therapy. J Urol.

Link:

Synthetic Lethal Metabolic Targeting of Senescent Cells after Androgen Deprivation Therapy

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