Parisi Alessandro, Rossi Francesca, De Filippis Chiara, Paoloni Francesco, Felicetti Cristiano, Mammarella Alex, Pecci Federica, Lupi Alessio, Berardi Rossana
Department of Clinical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero Universitaria delle Marche, Ancona, 60126, Italy.
Onco Targets Ther. 2023 Jul 18;16:585-613. doi: 10.2147/OTT.S272563. eCollection 2023.
In recent years, poly (ADP-ribose) polymerase (PARP) inhibition has become a promising therapeutic option for several tumors, especially for those harboring a BRCA 1-2 mutation or a deficit in the homologous recombination repair (HRR) pathway. Nevertheless, to date, PARP inhibitors are still not largely used for thoracic malignancies neither as a single agent nor in combination with other treatments. Recently, a deeper understanding of HRR mechanisms, alongside the development of new targeted and immunotherapy agents, particularly against HRR-deficient tumors, traced the path to new treatment strategies for many tumor types including lung cancer and malignant pleural mesothelioma. The aim of this review is to sum up the current knowledge about cancer-DNA damage response pathways inhibition and to update the status of recent clinical trials investigating the use of PARP inhibitors, either as monotherapy or in combination with other agents for the treatment of thoracic malignancies. We will also briefly discuss available evidence on Poly(ADP-Ribose) Glycohydrolase (PARG) inhibitors, a novel promising therapeutic option in oncology.
近年来,聚(ADP - 核糖)聚合酶(PARP)抑制已成为多种肿瘤颇具前景的治疗选择,尤其是对于那些携带BRCA 1 - 2突变或同源重组修复(HRR)途径存在缺陷的肿瘤。然而,迄今为止,PARP抑制剂在胸部恶性肿瘤中仍未广泛应用,无论是作为单一药物还是与其他治疗联合使用。最近,对HRR机制的更深入理解,以及新的靶向和免疫治疗药物的开发,特别是针对HRR缺陷肿瘤的药物,为包括肺癌和恶性胸膜间皮瘤在内的许多肿瘤类型开辟了新的治疗策略途径。本综述的目的是总结目前关于癌症 - DNA损伤反应途径抑制的知识,并更新近期临床试验的现状,这些试验研究了PARP抑制剂作为单一疗法或与其他药物联合用于治疗胸部恶性肿瘤的情况。我们还将简要讨论聚(ADP - 核糖)糖苷水解酶(PARG)抑制剂的现有证据,这是肿瘤学中一种新的有前景的治疗选择。