Innovative RAD51 Biomarker Enhances Personalized Treatments for Prostate Cancer

Recent research published in Cell Reports Medicine highlights the potential of a novel biomarker, RAD51, to improve the personalization of treatment for metastatic prostate cancer (mPC). Conducted by the Vall d'Hebron Institute of Oncology (VHIO), this study suggests that RAD51 testing could serve as a complementary tool to next-generation sequencing (NGS), enhancing the stratification of patients and guiding more effective treatment decisions.

Approximately 20% to 25% of advanced prostate cancer cases exhibit genomic alterations related to DNA damage repair (DDR) pathways, particularly involving homologous recombination repair (HRR) gene mutations. Recognizing the specific molecular features and targetable mutations within each tumor has become essential in the management of metastatic prostate cancer.

Precision medicine has made significant strides, particularly with the identification of HRR defects that correlate with patient responses to PARP inhibitors. However, the implementation of NGS testing in routine clinical practice faces several obstacles. Researchers at VHIO emphasize the need for refined biomarker strategies that could enhance patient stratification and treatment selection.

The RAD51 protein plays a critical role in the HRR process. The RAD51 assay, developed by researchers at VHIO, detects this protein as a functional biomarker, potentially improving the stratification of cancer patients with deficiencies in the DDR pathways. This functional approach may also streamline patient stratification efforts, particularly in situations where NGS testing is resource-constrained.

In this study, the researchers conducted a thorough analysis of HRR status using both NGS and the RAD51 test across 219 biopsies from 187 patients diagnosed with advanced prostate cancer. The genomic analysis revealed frequent alterations in several key genes, including TP53, PTEN, AR, MYC, BRCA2, ATM, and BRCA1, underscoring the complex genomic landscape of mPC.

Results indicated that 21% of the analyzed samples exhibited a low RAD51 score, indicating HRR deficiency. The RAD51 test demonstrated high sensitivity and specificity for identifying tumors with BRCA1/2 mutations. Patients with RAD51-low scores showed improved progression-free survival (PFS) when treated with PARP inhibitors or platinum-based chemotherapy, suggesting the biomarker's clinical utility.

The findings indicate that the RAD51 biomarker could effectively identify patients with HRR-defective prostate cancer who may benefit from targeted therapies. This approach could be particularly advantageous in clinical settings where tissue samples are limited, and traditional sequencing may not be feasible.