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[同源重组缺陷与聚(ADP-核糖)聚合酶抑制剂在治疗中的应用]

[Homologous recombination deficiency and PARP inhibitors in therapeutics].

作者信息

Salaün Hélène, Saint-Ghislain Mathilde, Bellesoeur Audrey, Beuzeboc Philippe, Neuzillet Cindy, Diéras Véronique, Stern Marc Henri, Rodrigues Manuel

机构信息

PSL research university, institut Curie, medical oncology department, 35, rue Dailly, 92210 Saint-Cloud, France.

PSL research university, institut Curie, medical oncology department, 26, rue d'Ulm, 75005 Paris, France.

出版信息

Bull Cancer. 2022 Jan;109(1):76-82. doi: 10.1016/j.bulcan.2021.09.015. Epub 2021 Nov 17.

Abstract

PARP inhibitors are effective in different types of tumors such as ovarian, breast, prostate and pancreatic cancer. Many studies are in progress and may lead to prescription evolution. PARP inhibitors prescription is almost reserved to patients with a constitutional BRCA mutation or a somatic BRCA alteration or a tumor with a deficiency in homologous recombination. Nowadays, the diagnosis of homologous recombination deficit, HRD, is possible with the prescription of a myChoice CDx (Myriad) test. PARP inhibitors are studied in association with chemotherapy and targeted therapies but also with radiotherapy and with immune checkpoint inhibitors. Access to PARP inhibitors is challenged with the emergence of resistance mechanism. Various trials are now studying the possibility of reversing these resistance mechanisms.

摘要

聚(ADP-核糖)聚合酶(PARP)抑制剂对多种类型的肿瘤有效,如卵巢癌、乳腺癌、前列腺癌和胰腺癌。许多研究正在进行中,可能会导致用药方案的演变。PARP抑制剂的处方几乎仅限于患有遗传性BRCA突变、体细胞BRCA改变或同源重组缺陷肿瘤的患者。如今,通过myChoice CDx(Myriad)检测可以诊断同源重组缺陷(HRD)。PARP抑制剂正在与化疗、靶向治疗联合进行研究,也在与放疗和免疫检查点抑制剂联合进行研究。随着耐药机制的出现,PARP抑制剂的使用受到了挑战。目前各种试验正在研究逆转这些耐药机制的可能性。

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