RAD51 as a Therapeutic Target and Predictive Biomarker in Breast Cancer Radiotherapy: A Systematic Review and Translational Synthesis

Abstract

Background: Treatment-resistant breast cancer (BC) is a significant clinical issue. The prognostic and predictive value of RAD51 expression in BC and radiotherapy (RT) remains inconsistent. This review examines the clinical and translational evidence regarding RAD51's role in BC risk and RT resistance, as well as its potential as a predictive biomarker and therapeutic target.

Main body:  This systematic review synthesised clinical and translational evidence on RAD51’s role in BC risk and RT resistance. A systematic literature search was conducted in PubMed, Scopus, Google Scholar, and IASJ (2014–2024) following PRISMA 2020 guidelines. Given the significant variability in study designs, outcome measures, and experimental models, a meta-analysis was not achievable. This review encompasses 25 studies. Seventeen studies have shown that RAD51 may be a therapeutic target for treatment-resistant BC cells in vitro and in vivo. Six studies revealed that RAD51 polymorphisms, rs1801320 (G>C) and rs1801321 (G>T), increase BC risk and RT resistance. Four studies reported that RAD51 may be a predictive and/or prognostic biomarker for BC development and therapeutic responses.

Conclusion: RAD51 overexpression correlates with BC development and radio-resistance. Downregulation radiosensitises tumour cells. RAD51 may serve as a predictive biomarker and represent a promising therapeutic target. RAD51 polymorphisms may influence RT response and BC risk. However, verification is needed.