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卵巢癌复发:铂耐药的定义是否因PARPi及其他干预治疗而改变?铂耐药卵巢癌治疗格局的演变

Ovarian cancer recurrence: is the definition of platinum resistance modified by PARPi and other intervening treatments? The evolving landscape in the management of platinum-resistant ovarian cancer.

作者信息

Flynn Michael J, Ledermann Jonathan A

机构信息

Department of Oncology, University College London Hospital, London NW1 2PG, United Kingdom.

UCL Cancer Institute, University College London, London WC1E 6DD, United Kingdom.

出版信息

Cancer Drug Resist. 2022 May 12;5(2):424-435. doi: 10.20517/cdr.2022.13. eCollection 2022.

Abstract

Definitions of platinum resistance have been questioned and changed over the last five years, even though no predictive biomarker of resistance exists. These have sculpted how we approach platinum retreatment and, consequently, how we devise new treatment strategies for those patients with tumour progression on platinum therapy. Platinum-non-eligible ovarian cancer is treated with single-agent non-platinum drugs. When bevacizumab can be added to chemotherapy, progression-free survival improves significantly. For patients with a BRCA mutation, PARP inhibitor monotherapy is an option compared to chemotherapy. There is currently no clearly identified role for immune-checkpoint inhibition in this patient population. This review describes some of the challenges in treating patients with platinum resistance and suggests refinements in the selection of patients most likely to benefit from targeting a DNA damage response, angiogenesis or immune modulation. It also describes novel agents of interest and possible mechanisms of the synergy of therapeutic combinations.

摘要

在过去五年中,铂耐药的定义一直受到质疑并有所改变,尽管不存在预测耐药的生物标志物。这些改变塑造了我们进行铂类再治疗的方式,进而也影响了我们为那些接受铂类治疗后肿瘤进展的患者设计新治疗策略的方式。铂类不适用的卵巢癌采用单药非铂类药物治疗。当贝伐单抗可添加到化疗中时,无进展生存期会显著改善。对于携带BRCA突变的患者,与化疗相比,PARP抑制剂单药治疗是一种选择。目前,免疫检查点抑制在这一患者群体中尚无明确的作用。本综述描述了治疗铂耐药患者的一些挑战,并建议在选择最有可能从靶向DNA损伤反应、血管生成或免疫调节中获益的患者方面进行改进。它还描述了有前景的新型药物以及治疗联合方案协同作用的可能机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba4e/9255242/286ac016abd5/cdr-5-2-424.fig.1.jpg

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