Giudice Elena, Gentile Marica, Salutari Vanda, Ricci Caterina, Musacchio Lucia, Carbone Maria Vittoria, Ghizzoni Viola, Camarda Floriana, Tronconi Francesca, Nero Camilla, Ciccarone Francesca, Scambia Giovanni, Lorusso Domenica
Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy.
Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Cancers (Basel). 2022 Mar 10;14(6):1420. doi: 10.3390/cancers14061420.
PolyADP-ribose polymerase (PARP) inhibitors (PARPis) represent the first clinically approved drugs able to provoke "synthetic lethality" in patients with homologous recombination-deficient (HRD) tumors. Four PARPis have just received approval for the treatment of several types of cancer. Besides, another three additional PARPis underlying the same mechanism of action are currently under investigation. Despite the success of these targeted agents, the increasing use of PARPis in clinical practice for the treatment of different tumors raised the issue of PARPis resistance, and the consequent disease relapse and dismal prognosis for patients. Several mechanisms of resistance have been investigated, and ongoing studies are currently focusing on strategies to address this challenge and overcome PARPis resistance. This review aims to analyze the mechanisms underlying PARPis resistance known today and discuss potential therapeutic strategies to overcome these processes of resistance in the future.
聚腺苷二磷酸核糖聚合酶（PARP）抑制剂（PARPis）是首批在临床上获得批准的、能够在同源重组缺陷（HRD）肿瘤患者中引发“合成致死”效应的药物。四种PARP抑制剂刚刚获批用于治疗多种类型的癌症。此外，另有三种作用机制相同的PARP抑制剂目前正在研究中。尽管这些靶向药物取得了成功，但PARP抑制剂在临床实践中用于治疗不同肿瘤的使用日益增加，这引发了PARP抑制剂耐药性的问题，以及随之而来的疾病复发和患者预后不良。已经对几种耐药机制进行了研究，目前正在进行的研究主要集中在应对这一挑战和克服PARP抑制剂耐药性的策略上。本综述旨在分析目前已知的PARP抑制剂耐药机制，并探讨未来克服这些耐药过程的潜在治疗策略。
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