Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA 22908, USA.
Int J Mol Sci. 2017 Oct 18;18(10):2171. doi: 10.3390/ijms18102171.
Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecologic malignancy. One of the leading causes of death in high-grade serous ovarian cancer (HGSOC) is chemoresistant disease, which may present as intrinsic or acquired resistance to therapies. Here we discuss some of the known molecular mechanisms of chemoresistance that have been exhaustively investigated in chemoresistant ovarian cancer, including drug efflux pump multidrug resistance protein 1 (MDR1), the epithelial-mesenchymal transition, DNA damage and repair capacity. We also discuss novel therapeutics that may address some of the challenges in bringing approaches that target chemoresistant processes from bench to bedside. Some of these new therapies include novel drug delivery systems, targets that may halt adaptive changes in the tumor, exploitation of tumor mutations that leave cancer cells vulnerable to irreversible damage, and novel drugs that target ribosomal biogenesis, a process that may be uniquely different in cancer versus non-cancerous cells. Each of these approaches, or a combination of them, may provide a greater number of positive outcomes for a broader population of HGSOC patients.
卵巢癌是女性癌症死亡的第五大主要原因，也是最致命的妇科恶性肿瘤。高级别浆液性卵巢癌 (HGSOC) 死亡的主要原因之一是化疗耐药性疾病，其可能表现为对治疗的内在或获得性耐药。在这里，我们讨论了一些已在耐药性卵巢癌中进行了详尽研究的已知化疗耐药分子机制，包括药物外排泵多药耐药蛋白 1 (MDR1)、上皮-间充质转化、DNA 损伤和修复能力。我们还讨论了一些新的治疗方法，这些方法可能解决了将针对化疗耐药过程的方法从实验室带到临床的一些挑战。其中一些新的治疗方法包括新型药物输送系统、可能阻止肿瘤适应性变化的靶标、利用使癌细胞易受不可逆损伤的肿瘤突变，以及针对核糖体生物发生的新型药物，该过程在癌症与非癌细胞中可能具有独特的差异。这些方法中的每一种，或它们的组合，都可能为更广泛的 HGSOC 患者群体带来更多的积极结果。
