Therapeutic Targeting of the Genome Guardian SIRTuins in Metastatic Prostate Cancer

Project Description Narrative:

Prostate cancer is the second leading cancer in the male population, with more than 250,000 new cases each year in the United States and more than 1.4 million new cases worldwide. Recent population health reports have indicated that the incidence rate of prostate cancer is on the rise, with an estimated 288,300 new cases and 34,700 deaths in the United States in 2023. While early diagnosis and treatment have led to a decline in the mortality rate of prostate cancer, the rate of decline has slowed down in recent years. Metastatic castration resistant prostate cancer and lethal neuroendocrine prostate cancer are the major contributors to the mortality.

The major risk factors for prostate cancer are age and race or ethnicity. African American and Caribbean men have 73% higher risk of developing prostate cancer and a 2.1-times higher likelihood of prostate cancer-related deaths than the average Caucasian man. The cost burden of metastatic prostate cancer is $5.2-$8.2 billion per year in the United States alone, steadily increasing over time. To address this issue, it is important to develop effective therapeutic interventions that utilize genomics-derived knowledge. This project aims to develop a novel therapy combination that simultaneously induces molecular vulnerability in metastatic prostate cancer and targets the induced molecular dependencies to render effective therapy regardless of racial or ethnic background and to promote health equity for all. If successful, the planned therapeutic benefits will immediately be accessible to advanced prostate cancer patients. The research outcome could directly or indirectly improve these patients' and their families' quality of life and potentially benefit others beyond the state.