Drug resistance in ovarian cancer: from mechanism to clinical trial

作者：Ling Wang, Xin Wang, Xueping Zhu, Lin Zhong, Qingxiu Jiang, Ya Wang, Qin Tang, Qiaoling Li, Cong Zhang, Haixia Wang, Dongling Zou · 发表于：Molecular Cancer · 年份：2024 · DOI：10.1186/s12943-024-01967-3 · 被引用次数：264 · 研究领域：MicroRNA in disease regulation、Cancer-related molecular mechanisms research、Epigenetics and DNA Methylation

Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical practice. We reviewed the literature regarding various drug resistance mechanisms in ovarian cancer and found that the main resistance mechanisms are as follows: abnormalities in transmembrane transport, alterations in DNA damage repair, dysregulation of cancer-associated signaling pathways, and epigenetic modifications. DNA methylation, histone modifications and noncoding RNA activity, three key classes of epigenetic modifications, constitute pivotal mechanisms of drug resistance. One drug can have multiple resistance mechanisms. Moreover, common chemotherapies and targeted drugs may have cross (overlapping) resistance mechanisms. MicroRNAs (miRNAs) can interfere with and thus regulate the abovementioned pathways. A subclass of miRNAs, "epi-miRNAs", can modulate epigenetic regulators to impact therapeutic responses. Thus, we also reviewed the regulatory influence of miRNAs on resistance mechanisms. Moreover, we summarized recent phase I/II clinical trials of novel drugs for ovarian cancer based on the abovementioned resistance mechanisms. A multitude of new therapies are unde...