Montaldo Nicola P, Nilsen Hilde Loge, Bordin Diana L
Department of Microbiology, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway; CRESCO - Centre for embryology and healthy Development, University of Oslo, Norway.
Department of Microbiology, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway; CRESCO - Centre for embryology and healthy Development, University of Oslo, Norway.
DNA Repair (Amst). 2025 May;149:103844. doi: 10.1016/j.dnarep.2025.103844. Epub 2025 May 9.
Targeting the DNA damage response (DDR) is a key strategy in cancer therapy, leveraging tumour-specific weaknesses in DNA repair pathways to enhance treatment efficacy. Traditional treatments, such as chemotherapy and radiation, use a broad, damage-inducing approach, whereas precision oncology aims to tailor therapies to specific genetic mutations or vulnerabilities. The clinical success of PARP inhibitors has renewed the interest in targeting DNA repair as a therapeutic strategy. Expanding the precision oncology toolbox by targeting the base excision repair (BER) pathway presents a promising avenue for cancer therapy, particularly in tumours that rely heavily on this pathway due to deficiencies in other DNA repair mechanisms. This review discusses how targeting BER could improve treatment outcomes, particularly in DDR-defective cancers. With ongoing advancements in biomarker discovery and drug development, BER-targeted therapies hold significant potential for refining precision oncology approaches.
靶向DNA损伤反应（DDR）是癌症治疗的关键策略，利用DNA修复途径中肿瘤特异性的弱点来提高治疗效果。传统治疗方法，如化疗和放疗，采用广泛的损伤诱导方法，而精准肿瘤学旨在针对特定的基因突变或弱点量身定制治疗方案。PARP抑制剂的临床成功重新激发了人们将靶向DNA修复作为一种治疗策略的兴趣。通过靶向碱基切除修复（BER）途径来扩展精准肿瘤学工具箱，为癌症治疗提供了一条有前景的途径，特别是对于那些由于其他DNA修复机制缺陷而严重依赖该途径的肿瘤。本文综述了靶向BER如何改善治疗效果，特别是在DDR缺陷型癌症中。随着生物标志物发现和药物开发的不断进步，靶向BER的疗法在完善精准肿瘤学方法方面具有巨大潜力。
