PARP抑制剂在乳腺癌中的治疗进展与应用
Therapeutic advances and application of PARP inhibitors in breast cancer.
作者信息
Zhou Teng, Zhang Jian
机构信息
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China.
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China.
出版信息
Transl Oncol. 2025 Jul;57:102410. doi: 10.1016/j.tranon.2025.102410. Epub 2025 May 12.
Targeting of DNA repair pathway is the main therapeutic approach for BRCA1 and BRCA2 associated tumors, including breast cancer. BRCA1/2 genes play a pivotal role in HRR pathway. Mutations in BRCA1/2 leads to DDR deficiency, which cause the increasing of genome instability, thus rendering cancer cells vulnerable to inhibition of DNA repair related proteins, such as PARP1. Pre-clinical studies has demonstrated that cancer cells with BRCA1/2 deficient are sensitive to PARPi, which are an emerging class of small molecule drug. Several clinical trials demonstrated the promising efficacy of PARP inhibitors for BRCA1/2 mutated breast cancer patient through selectively induce synthetic lethality cancer cells. Currently, four PARP inhibitors had been approved by FDA for clinical use. PARPi demonstrated to improve progression-free survival, while resistance to PARPi is inevitable. In this review article, we highlighted the advances in the PARPi clinical trials, resistance mechanism and coping strategies in breast cancer patients. We also summarized the international guideline and recommendations on PARP inhibitor usage in breast cancer.
靶向DNA修复途径是治疗包括乳腺癌在内的与BRCA1和BRCA2相关肿瘤的主要治疗方法。BRCA1/2基因在同源重组修复(HRR)途径中起关键作用。BRCA1/2的突变导致DNA损伤应答(DDR)缺陷,进而导致基因组不稳定性增加,从而使癌细胞易受DNA修复相关蛋白(如PARP1)抑制的影响。临床前研究表明,BRCA1/2缺陷的癌细胞对PARP抑制剂(PARPi)敏感,PARP抑制剂是一类新兴的小分子药物。多项临床试验表明,PARP抑制剂通过选择性诱导癌细胞合成致死,对BRCA1/2突变的乳腺癌患者具有良好的疗效。目前,有四种PARP抑制剂已获美国食品药品监督管理局(FDA)批准用于临床。PARPi已被证明可改善无进展生存期,然而,对PARPi产生耐药是不可避免的。在这篇综述文章中,我们重点介绍了PARPi在乳腺癌患者临床试验中的进展、耐药机制及应对策略。我们还总结了关于PARP抑制剂在乳腺癌中使用的国际指南和建议。