New Insights into Targeted Therapy for Aggressive Prostate Cancer

Overview
Recent findings from a Phase 2 clinical trial conducted at UC Davis Comprehensive Cancer Center have unveiled critical insights regarding the treatment of aggressive prostate cancer. The trial highlights the potential of specific biomarkers in developing tailored therapies for patients facing high recurrence rates of this disease.

The study, which will be presented at the upcoming American Society of Clinical Oncology (ASCO) conference, emphasizes the importance of personalized medicine in addressing the complexities of prostate cancer.

Trial Details
Researchers explored the efficacy of a drug known as niraparib (ZEJULA), which is administered prior to surgical intervention for prostate cancer. The objective was to assess whether this PARP inhibitor could reduce the likelihood of cancer recurrence in men diagnosed with aggressive forms of the disease, particularly those harboring specific DNA repair gene mutations.

The pilot study involved 11 participants with high-risk prostate cancer and particular biomarkers, including gene mutations. Each individual received a daily dosage of 200 mg of niraparib for a period of 90 days leading up to their surgery.

The cohort had a median age of 68 years, with a median prostate-specific antigen (PSA) level of 10.7 ng/mL at the time of diagnosis. Genetic alterations among the participants included inherited mutations in BRCA2, MSH6, and CHEK2, as well as somatic mutations in genes such as ATM, SPOP, KMT2C, and KMT2D.

Complexities of Prostate Cancer
While the administration of niraparib did not result in significant tumor shrinkage prior to surgery, the trial underscored the value of genetic testing and blood monitoring in comprehending and tracking the progression of prostate cancer. Notably, analyses of circulating tumor DNA (ctDNA) proved instrumental in detecting tumor evolution and resistance mechanisms in real-time.

According to Marc Dall'Era, the chief of the Urologic Surgery Department at UC Davis Health and the lead researcher of the study, the findings reflect the multifaceted nature of prostate cancer, particularly in patients with certain genetic mutations. Despite variable responses to treatment, especially among individuals with BRCA2 mutations, the study indicates that ctDNA could serve as a promising tool for identifying candidates who may benefit from targeted neoadjuvant therapies.

The research team is committed to further analyzing the data to unravel the reasons behind treatment resistance and to formulate future therapeutic strategies that are more customized to individual patient profiles.

The clinical trial was funded by Jannsen Pharmaceuticals and involved collaboration among several researchers, including Primo Lara Jr., Nicholas Mitsiades, Mamta Parikh, John McPherson, Kenneth Iczkowski, Irene Mitsiades, and Aedric Lim.