Grant: Travel Awards - Institute Community Support

Most primary prostate cancer responds well to surgery, but ~10% of men relapse with a more aggressive form of the disease known as castration-resistant prostate cancer (CRPC). Currently, there are no approved methods for predicting which localized tumors are most likely to recur. The two main stages of prostate cancer (primary localized & late-stage CRPC) have been independently well studied; however, few projects have described the genetic changes that occur in prostate tumors over the course of disease progression. This is due in part to the difficulty of obtaining DNA samples that reflect the tumor genetic landscape before, during and after CRPC relapse. There remains an unmet need to characterize the full evolutionary development of these tumors, spanning early diagnosis to late-stage recurrence of advanced disease. Our objective was to identify the characteristics of primary prostate tumors that signify an increased likelihood of relapse. For each patient, we extracted DNA from tumor tissue that had been previously obtained during surgical removal of the prostate. We also isolated tumor DNA from the blood of these same patients, who had now relapsed with CRPC. This technique, known as a "liquid biopsy", is possible because dying tumor cells are constantly shedding DNA into the patient's bloodstream. The DNA from both early and late-stage disease for each patient was profiled, and from it we identified several key genetic mutations that were present in both time points. These data offer insight into the mutations that may be driving progression to CRPC, and could eventually serve as indicators of those primary tumors carrying an increased risk of relapse post-surgery. This knowledge would allow clinicians to recognize which patients should be closely monitored in following years, and if necessary, prioritize them for rapid therapeutic intervention in the case of cancer resurgence.