前列腺癌是美国男性癌症死亡的第二大原因。根据前列腺癌的组织病理亚型，可用多种治疗选择，如雄激素剥夺疗法（ADT）、雄激素受体信号抑制剂（ARSI）、免疫疗法和化疗来治疗前列腺癌。虽然这些治疗在治疗的初期阶段有效，但肿瘤随后对这些治疗产生耐药性。尽管到目前为止已取得了诸多进展，但治疗耐药仍然是前列腺癌治疗中的一大挑战。尽管已报道了多种导致前列腺癌耐药发展的机制，但基因直接或间接涉及药物反应途径的改变表达是常见的事件。除了基因调控的遗传基础（如突变和基因扩增）外，表观遗传变化与基因异常表达频繁地与癌症的发生、发展以及治疗耐药发展有关。虽然有一些综述文章汇编了与前列腺癌治疗耐药有关的遗传机制的报道，但尚未有综述文章总结前列腺癌治疗耐药发展中的表观遗传机制。因此，本文的目的是整理各种报道并提供关于表观遗传异常，以及表观遗传机制引起的基因异常表达在鳞状细胞前列腺癌（CRPCs）和治疗耐药发展中的综合综述。此外，根据临床试验结果，还讨论了基于表观遗传的治疗在化疗难治性前列腺癌治疗中的潜力。版权所有©2023 Elsevier Inc.

Prostate cancer is the second leading cause of cancer death among men in the United States. Depending upon the histopathological subtypes of prostate cancers, various therapeutic options, such as androgen deprivation therapy (ADT), androgen receptor signaling inhibitors (ARSI), immunotherapy, and chemotherapy, are available to treat prostate cancer. While these therapeutics are effective in the initial stages during treatments, the tumors subsequently develop resistance to these therapies. Despite all the progress made so far, therapeutic resistance remains a major challenge in the treatment of prostate cancer. Although various mechanisms have been reported for the resistance development in prostate cancer, altered expression of genes either directly or indirectly involved in drug response pathways is a common event. In addition to the genetic basis of gene regulation such as mutations and gene amplifications, epigenetic alterations involved in the aberrant expression of genes have frequently been shown to be associated not only with cancer initiation and progression but also with therapeutic resistance development. There are several review articles compiling reports on genetic mechanisms involved in therapeutic resistance in prostate cancer. However, epigenetic mechanisms for the therapeutic resistance development in prostate cancer have not yet been summarized in a review article. Therefore, the objective of this article is to compile various reports and provide a comprehensive review of the epigenetic aberrations, and aberrant expression of genes by epigenetic mechanisms involved in CRPCs and therapeutic resistance development in prostate cancer. Additionally, the potential of epigenetic-based therapeutics in the treatment of chemorefractory prostate cancer as evidenced by clinical trials has also been discussed.Copyright © 2023. Published by Elsevier Inc.