Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China.
Cancer Control. 2024 Jan-Dec;31:10732748241298329. doi: 10.1177/10732748241298329.
The application of PARP inhibitors has revolutionized cancer treatment and has achieved significant advancements, particularly with regard to tumors with defects in genes involved in homologous recombination repair (HRR) processes, such as BRCA1 and BRCA2. Despite the promising outcomes of PARP inhibitors, certain limitations and challenges still exist, including acquired drug resistance, severe side effects, and limited therapeutic benefits for patients without homologous recombination deficiency (HRD). Various combinations involving PARP inhibitors have been developed to overcome these limitations. Among these, combinations with immune checkpoint inhibitors, antiangiogenic agents, and various small-molecule inhibitors are well-studied strategies that show great potential for optimizing the efficacy of PARP inhibitors, overcoming resistance mechanisms, and expanding target populations. However, the efficiency and overlapping toxicity of these combination strategies for cancers vary among studies, thereby limiting their use. In this review, we describe the mechanisms and limitations of PARP inhibitors to better understand the mechanisms of combination treatments. Furthermore, we have summarized recent studies on the combination of PARP inhibitors with a range of medications and discussed their clinical efficacy. The objective of this review is to enhance the comprehensiveness of information pertaining to this topic.
PARP 抑制剂的应用彻底改变了癌症治疗，并取得了重大进展，特别是对于涉及同源重组修复（HRR）过程中基因缺陷的肿瘤，如 BRCA1 和 BRCA2。尽管 PARP 抑制剂有很好的疗效，但仍存在一些局限性和挑战，包括获得性耐药性、严重的副作用，以及对于没有同源重组缺陷（HRD）的患者的治疗获益有限。已经开发了各种涉及 PARP 抑制剂的联合治疗方案来克服这些局限性。其中，与免疫检查点抑制剂、抗血管生成药物和各种小分子抑制剂联合使用是研究较多的策略，这些策略显示出了优化 PARP 抑制剂疗效、克服耐药机制和扩大目标人群的巨大潜力。然而，这些联合治疗策略在癌症中的效率和重叠毒性在不同的研究中有所不同，从而限制了它们的应用。在这篇综述中，我们描述了 PARP 抑制剂的作用机制和局限性，以便更好地理解联合治疗的机制。此外，我们还总结了最近关于 PARP 抑制剂与一系列药物联合应用的研究，并讨论了它们的临床疗效。本文的目的是增强对这一主题的全面了解。
