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 under evaluation, and the preliminary results are encouraging. This review provides new insight into the classification of drug resistance mechanisms in ovarian cancer and may facilitate in the successful treatment of resistant ovarian cancer.

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卵巢癌的耐药性：从机制到临床试验

卵巢癌是妇科癌症相关死亡的主要原因。耐药性是卵巢癌治疗的瓶颈。新药在临床实践中的使用日益增多，给耐药卵巢癌的治疗带来了挑战。在不了解其潜在机制的情况下继续根据药物类型对耐药性进行分类，不适合当前的临床实践。我们回顾了有关卵巢癌各种耐药机制的文献，发现主要的耐药机制如下：跨膜转运异常、DNA损伤修复改变、癌症相关信号通路失调和表观遗传修饰。 DNA 甲基化、组蛋白修饰和非编码 RNA 活性这三类关键的表观遗传修饰构成了耐药性的关键机制。一种药物可以有多种耐药机制。而且，常见的化疗药物和靶向药物可能存在交叉（重叠）耐药机制。 MicroRNA (miRNA) 可以干扰并调节上述途径。 miRNA 的一个子类“epi-miRNA”可以调节表观遗传调节因子以影响治疗反应。因此，我们还回顾了 miRNA 对耐药机制的调节影响。此外，我们还根据上述耐药机制总结了近期针对卵巢癌新药的I/II期临床试验。多种新疗法正在评估中，初步结果令人鼓舞。该综述为卵巢癌耐药机制的分类提供了新的见解，并可能有助于成功治疗耐药性卵巢癌。