Establishing a Biomarker Discovery Platform to Track Progression to Treatment Resistant Neuroendocrine Prostate Cancer

Prostate cancer (PC) remains the most common cancer among North American men, with many cases progressing to castration-resistant prostate cancer (CRPC) despite androgen-deprivation therapy. A significant subset of these patients further develops neuroendocrine prostate cancer (NEPC), a highly aggressive and treatment-resistant form of the disease. Early identification of NEPC is crucial to improving patient outcomes, yet current diagnostic methods rely on invasive biopsies that are not routinely performed during disease progression. This study aims to establish a biomarker discovery platform to evaluate circulating tumor RNA (ctRNA) as a non-invasive diagnostic tool for tracking the progression from CRPC to NEPC. Using blood, saliva, and urine samples from prostate cancer patients, we will conduct whole transcriptome sequencing (WTS) to assess whether ctRNA accurately reflects tumor RNA profiles. We will specifically analyze molecular signatures associated with NEPC, including key cell cycle regulators, to determine the feasibility of ctRNA-based diagnostics. Preliminary findings suggest that NEPC exhibits a distinct cell cycle signature that we hypothesize can be detected in ctRNA. If successful, this study will justify a large-scale clinical trial to evaluate the use of liquid biopsies for early NEPC detection. Establishing ctRNA as a biomarker could significantly enhance personalized treatment strategies, enabling earlier intervention, improving survival outcomes, and reducing unnecessary treatments. This pilot study represents a critical step toward transforming prostate cancer management through non-invasive biomarker discovery.