卵巢癌PARP抑制剂联合治疗的前景
Perspectives on PARP Inhibitor Combinations for Ovarian Cancer.
作者信息
Bonadio Renata Colombo, Estevez-Diz Maria Del Pilar
机构信息
Instituto do Cancer do Estado de Sao Paulo, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
Medical Oncology, Oncologia D'Or, Sao Paulo, Brazil.
出版信息
Front Oncol. 2021 Dec 15;11:754524. doi: 10.3389/fonc.2021.754524. eCollection 2021.
Poly (ADP-ribose) polymerase (PARP) inhibitors constitute an important treatment option for ovarian cancer nowadays. The magnitude of benefit from PARP inhibitors is influenced by the homologous recombination status, with greater benefit observed in patients with BRCA mutated or BRCA wild-type homologous recombination deficient (HRD) tumors. Although some PARP inhibitor activity has been shown in homologous recombination proficient (HRP) ovarian tumors, its clinical relevance as a single agent is unsatisfactory in this population. Furthermore, even HRD tumors present primary or secondary resistance to PARP inhibitors. Strategies to overcome treatment resistance, as well as to enhance PARP inhibitors' efficacy in HRP tumors, are highly warranted. Diverse combinations are being studied with this aim, including combinations with antiangiogenics, immunotherapy, and other targeted therapies. This review discusses the rationale for developing therapy combinations with PARP inhibitors, the current knowledge, and the future perspectives on this issue.
聚(ADP - 核糖)聚合酶(PARP)抑制剂如今已成为卵巢癌的一种重要治疗选择。PARP抑制剂的获益程度受同源重组状态影响,在携带BRCA突变或BRCA野生型同源重组缺陷(HRD)肿瘤的患者中观察到更大的获益。尽管在同源重组 proficient(HRP)卵巢肿瘤中已显示出一些PARP抑制剂活性,但其作为单一药物在该人群中的临床相关性并不令人满意。此外,即使是HRD肿瘤也会对PARP抑制剂产生原发性或继发性耐药。克服治疗耐药以及提高PARP抑制剂在HRP肿瘤中的疗效的策略非常必要。为此正在研究多种联合方案,包括与抗血管生成药物、免疫疗法及其他靶向疗法的联合。本综述讨论了开发PARP抑制剂联合疗法的理论依据、当前的认识以及该问题的未来展望。