| 罗裕银,王祥琳,罗德红.DNA损伤修复在乳腺癌治疗抵抗中的研究进展[J].肿瘤学杂志,2025,31(9):763-768. |
| DNA损伤修复在乳腺癌治疗抵抗中的研究进展 |
| Research Progress on DNA Damage Repair and Therapeutic Resistance in Breast Cancer |
| 投稿时间：2024-11-09 |
| DOI：10.11735/j.issn.1671-170X.2025.09.B003 |
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| 中文关键词: 乳腺肿瘤 DNA损伤修复 治疗抵抗 |
| 英文关键词:breast neoplasms DNA damage repair treatment resistance |
| 基金项目: |
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| 摘要点击次数: 153 |
| 全文下载次数: 76 |
| 中文摘要: |
| 摘 要：乳腺癌治疗抵抗是临床工作中的一个巨大挑战，乳腺癌治疗抵抗与DNA损伤修复机制密切相关。DNA损伤后由非同源末端连接、同源重组、碱基切除修复、核苷酸切除修复、错配修复、跨损伤DNA合成、微同源介导的末端连接、特定的酶和蛋白质几个关键修复通路共同发挥作用，以维护基因组稳定性及细胞正常功能。全文综述DNA修复通路的异质性，分析乳腺癌患者DNA损伤后不同修复途径的差异性，探讨抑制DNA损伤修复研究进展及策略；同时指出抑制DNA损伤修复存在DNA修复通路复杂性、乳腺癌异质性、正常组织治疗限制性等问题，未来可向分子标志物、基因组学、特异性抑制剂、精准治疗和联合治疗等展开研究，以降低治疗抵抗，改善乳腺癌患者预后，推动治疗向个体化、精准化方向发展。 |
| 英文摘要: |
| Abstract： Therapeutic resistance remains a major challenge in the clinical management of breast cancer and is closely associated with DNA damage repair (DDR) mechanisms. Multiple DDR pathways—including non-homologous end joining (NHEJ)， homologous recombination (HR)， base excision repair (BER)， nucleotide excision repair (NER)， mismatch repair (MMR)， translesion DNA synthesis (TLS)， microhomology-mediated end joining (MMEJ)， and the involvement of specific enzymes and proteins—act in concert to maintain genomic integrity and cellular function following DNA damage. This review summarizes the heterogeneity of DNA repair pathways， analyzes differential repair activities in breast cancer patients， and discusses recent advances and strategies in targeting DDR to overcome treatment resistance. However， challenges such as the complexity of repair pathways， tumor heterogeneity， and toxicity to normal tissues limit the clinical application of DDR inhibitors. Future research should focus on identifying molecular biomarkers， leveraging genomic data， developing specific inhibitors， implementing precision radiotherapy， exploring combination therapies， and designing individualized treatment strategies to mitigate resistance and improve patient outcomes. |
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