Investigating the Potential of Repurposing Anti-Diabetic/Obesity Drugs for the Treatment of Obesity-Driven Aggressive Prostate Cancer
Description: Obesity is a global epidemic that will soon overtake smoking as the largest preventable risk factor for cancer. Every five-point increase in body-mass index increases risk of fatal prostate cancer (PC) by almost 10% and shortens the time to develop castration-resistance. However, mechanisms underpinning obesity-driven prostate cancer remain poorly understood.
The prostate is surrounded by peri-prostatic adipose tissue (PPAT), and greater amounts of PPAT are associated with increased risk of lethal prostate cancer and reduced therapy-response. PPAT secretes hormones, adipokines/cytokines, and extracellular vesicles (EVs), which are tiny particles that transfer cargo including protein, lipids, metabolites and RNA from the parent cell to distant sites. These PPAT-secreted factors can promote the progression of other cancer types and deserve study in prostate cancer.
Dr. Nil Grunberg is investigating how PPAT-secreted factors drive prostate cancer tumorigenesis, and whether FDA-approved anti-diabetic/obesity drugs (ADODs) such as Semaglutide, Tirzepatide and Metformin, can impact these factors and prevent prostate cancer progression.
The mechanisms behind ADOD reprogramming of PPAT adipocytes and the impact they have on prostate cancer cells will be investigated in matched patient PPAT/tumor tissues and genetically-engineered mouse models.
The effects of ADODs on prostate cancer cell behavior and agressiveness and whether treatment with ADODs can inhibit obesity-associated prostate cancer progression will be determined in models.
If successful, this project will illuminate the mechanisms by which peri-prostatic adipose tissue drives prostate cancer progression, and whether diabetic/obesity drugs can be repurposed as a cancer therapeutic, particularly in obese patients.
What this means to patients:
Obesity is a strong risk factor for prostate cancer development, progression, and mortality. Peri-prostatic adipose tissue (PPAT) is also associated with increased risk of lethal prostate cancer and reduced therapy-response. Dr. Grunberg’s project will improve knowledge of how obesity and PPAT drive prostate cancer, and determine the potential of Semaglutide/Tirzepatide as anti-cancer medications that could be combined with standard prostate cancer treatment in obese patients to reduce risk of increased mortality, cut treatment costs, and improve quality of life.
Funder: Prostate Cancer Foundation
Funding type: research
Funder scheme: PCF Young Investigator Award
Start date: 2024-01-01
Investigators: Nil Grunberg, Nil Grunberg
Institution: Imperial College London
Funded outputs count: 0
Funder award ID: PCF-116806
OpenAlex ID: G9000444586