About me
Investigating how obesity and metabolic dysfunction promote prostate cancer progression
Location: 41
Mentor: Dr. Priyamvada Rai
Prostate cancer (PC) is the second leading cancer-related killer of American men and in its early stage is referred to as castration-sensitive prostate cancer (CSPC). In 20-40% of patients, it progresses to metastatic disease due to treatment failure, where androgen deprivation therapy (ADT), the current standard of care becomes required. ADT inevitably fails, resulting in castration-resistant prostate cancer (CRPC), which is incurable and fatal. Majority of PC patients in the US are overweight and suffer from pre-existing metabolic syndrome, which is exacerbated by ADT, increasing treatment-related morbidity and mortality risk. Since obesity drives progression, these patients are more likely to need ADT and to die of ADT. The goal of this study is to investigate how molecular factors associated with diet-driven obesity promote PC incidence and growth, in order to identify complementary or alternative treatment strategies to ADT to protect PC patients against treatment-induced cardiotoxicity. We injected LNCaP CSPC cells into gonadally intact athymic animals fed either a Western diet (60% fat) or a matched standard diet. We found that animals on the western diet have more and larger xenograft tumors, higher weights and cholesterol, which could not be accounted for by changes in testosterone levels. Novel hypoxia and inflammatory factors associated with diet driven obesity were also identified. Understanding these metabolic implications allows for the development of new clinically actionable strategies that address the metabolic dysfunction in PC patients and limit PC progression, so overweight or obese patients don’t progress to the point of needing ADT.
