Deoxyribonucleic acid (DNA) recombination between homologous chromosomes is essential in the process of meiosis as it drives genetic diversity and assures accurate segregation. In somatic cells, a substantial machinery is involved in DNA damage repair (DDR). Failure to repair DNA damage has many consequences, including cancer predisposition. Insights in DDR mechanisms and the prevalence of defects in DDR in tumours has resulted in the fundamental insight of the presence of DDR defects as a chemosensitising biomarker for alkylating agents in high-grade serous ovarian cancer, non-small-cell lung cancer and glioblastoma. Increasing the DDR defect by PARP inhibition in this context of pre-existing DDR impairment, can result in catastrophic DNA damage and cancer cell death. In patients with mCRPC and demonstrated intratumoural DDR defect, PARP inhibition represents a valuable new treatment option.
(BELG J MED ONCOL 2021;15(4):164-9)