Department of Oncology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Pediatric Clinic No. 2, Department of Pediatric CNardiology, Emergency County Hospital for Children, 400177 Cluj-Napoca, Romania.
Medicina (Kaunas). 2023 Mar 10;59(3):544. doi: 10.3390/medicina59030544.
Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor prognosis and few treatment options with limited efficacy. Resistance to platinum compounds is a complex process involving multiple mechanisms pertaining not only to the tumoral cell but also to the tumoral microenvironment. In this review, we discuss the molecular mechanism involved in ovarian cancer cells' resistance to platinum-based chemotherapy, focusing on the alteration of drug influx and efflux pathways, DNA repair, the dysregulation of epigenetic modulation, and the involvement of the tumoral microenvironment in the acquisition of the platinum-resistant phenotype. Furthermore, we review promising alternative treatment approaches that may improve these patients' poor prognosis, discussing current strategies, novel combinations, and therapeutic agents.
卵巢癌是致死率最高的妇科恶性肿瘤。铂类化疗是卵巢癌治疗的基础，尽管大多数患者最初患有铂类敏感疾病，但经过多次复发，他们将产生耐药性。铂耐药性复发性卵巢癌预后不良，治疗选择有限，疗效有限。铂类化合物耐药是一个复杂的过程，涉及多种机制，不仅与肿瘤细胞有关，还与肿瘤微环境有关。在这篇综述中，我们讨论了涉及卵巢癌细胞对铂类化疗耐药的分子机制，重点讨论了药物摄取和外排途径的改变、DNA 修复、表观遗传调节的失调以及肿瘤微环境在获得铂耐药表型中的作用。此外，我们还综述了有希望改善这些患者不良预后的替代治疗方法，讨论了当前的策略、新的联合治疗和治疗药物。
