在癌症中经常观察到改变的表观遗传图谱，最近的研究表明表观修饰在多种抗癌药物，包括DNA损伤剂的反应中扮演着重要的角色。拓扑异构酶I（Top I）是一个着名的核酶，对于DNA的功能和细胞生存至关重要，其抑制会引起DNA链断裂和细胞周期阻滞。人类Top I的抑制剂已被证明是大量癌症患者繁荣的化学治疗方法。虽然该治疗对许多病例是有效的，但耐药性和改变的细胞反应仍然是主要的治疗问题。本综述强调了截至目前为止关于不同表观遗传修饰对Top I抑制剂反应影响以及靶向表观遗传变化来提高Top I抑制剂疗效和安全性的证据。表观遗传研究领域正在稳步增长。通过它的帮助，我们可以更好地理解药物反应和耐药性如何工作。表观遗传学可以发展为许多药物，包括Top I抑制剂的可能生物标志物和预测因子，并可能具有需要更深入关注的重要临床意义。 要点： 表观遗传修改，包括DNA甲基化和组蛋白修饰，在多种抗癌治疗，包括Top I抑制剂等DNA损伤剂的反应中发挥着重要作用。尽管倍半萜衍生物在临床上被用作Top I抑制剂治疗癌症，但某些类型的癌症具有内在性和/或获得性耐药性，限制了它们的治疗潜力。DNA低甲基化等表观遗传修饰可以通过不同的机制增加或减少对Top I抑制剂的敏感性。Top I抑制剂与组蛋白修饰酶抑制剂的联合使用可以导致增强的细胞毒性效应并使抵抗细胞对Top I抑制剂产生敏感性。miRNA发现直接影响癌细胞中Top I和其他蛋白质的表达，从而对Top I抑制剂的反应产生积极或消极的改变。 lncRNA及其遗传多态性已发现与Top I功能和对其抑制剂的反应有关。表观遗传药物与Top I抑制剂的联合临床试验非常丰富，其中一些显示出潜在的有希望的结果。

Altered epigenetic map is frequently observed in cancer and recent investigations have demonstrated a pertinent role of epigenetic modifications in the response to many anticancer drugs including the DNA damaging agents. Topoisomerase I (Top I) is a well-known nuclear enzyme that is critical for DNA function and cell survival and its inhibition causes DNA strand breaks and cell cycle arrest. Inhibitors of human Top I have proven to be a prosperous chemotherapeutic treatment for a vast number of cancer patients. While the treatment is efficacious in many cases, resistance and altered cellular response remain major therapeutic issues.This review highlights the evidence available till date on the influence of different epigenetic modifications on the response to Top I inhibitors as well as the implications of targeting epigenetic alterations for improving the efficacy and safety of Top I inhibitors.The field of epigenetic research is steadily growing. With its assistance, we could gain better understanding on how drug response and resistance work. Epigenetics can evolve as possible biomarkers and predictors of response to many medications including Top I inhibitors, and could have significant clinical implications that necessitate deeper attention.HIGHLIGHTSEpigenetic alterations, including DNA methylation and histone modifications, play a pertinent role in the response to several anticancer treatments, including DNA damaging agents like Top I inhibitors.Although camptothecin derivatives are used clinically as Top I inhibitors for management of cancer, certain types of cancer have inherent and or acquired resistance that limit the curative potential of them.Epigenetic modifications like DNA hypomethylation can either increase or decrease sensitivity to Top I inhibitors by different mechanisms.The combination of Top I inhibitors with the inhibitors of histone modifying enzymes can result in enhanced cytotoxic effects and sensitization of resistant cells to Top I inhibitors.MicroRNAs were found to directly influence the expression of Top I and other proteins in cancer cells resulting in positive or negative alteration of the response to Top I inhibitors.lncRNAs and their genetic polymorphisms have been found to be associated with Top I function and the response to its inhibitors.Clinical trials of epigenetic drugs in combination with Top I inhibitors are plentiful and some of them showed potentially promising outcomes.