Gachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, Republic of Korea.
Exp Mol Med. 2023 Jul;55(7):1333-1347. doi: 10.1038/s12276-023-01014-z. Epub 2023 Jul 3.
The development and immune evasion of cancer stem cells (CSCs) limit the efficacy of currently available anticancer therapies. Recent studies have shown that epigenetic reprogramming regulates the expression of characteristic marker proteins and tumor plasticity associated with cancer cell survival and metastasis in CSCs. CSCs also possess unique mechanisms to evade external attacks by immune cells. Hence, the development of new strategies to restore dysregulated histone modifications to overcome cancer resistance to chemotherapy and immunotherapy has recently attracted attention. Restoring abnormal histone modifications can be an effective anticancer strategy to increase the therapeutic effect of conventional chemotherapeutic and immunotherapeutic drugs by weakening CSCs or by rendering them in a naïve state with increased sensitivity to immune responses. In this review, we summarize recent findings regarding the role of histone modifiers in the development of drug-resistant cancer cells from the perspectives of CSCs and immune evasion. In addition, we discuss attempts to combine currently available histone modification inhibitors with conventional chemotherapy or immunotherapy.
癌症干细胞 (CSC) 的发展和免疫逃逸限制了目前可用的抗癌疗法的疗效。最近的研究表明，表观遗传重编程调节特征标记蛋白的表达和与 CSC 中癌细胞存活和转移相关的肿瘤可塑性。CSC 还具有独特的机制来逃避免疫细胞的外部攻击。因此，最近人们关注开发新策略来恢复失调的组蛋白修饰，以克服癌症对化疗和免疫疗法的耐药性。恢复异常的组蛋白修饰可以成为一种有效的抗癌策略，通过削弱 CSC 或使其处于对免疫反应更敏感的幼稚状态，增加常规化疗和免疫治疗药物的治疗效果。在这篇综述中，我们从 CSC 和免疫逃逸的角度总结了组蛋白修饰剂在耐药性癌细胞发展中的作用的最新发现。此外，我们还讨论了尝试将现有的组蛋白修饰抑制剂与常规化疗或免疫疗法相结合的方法。
