In hormone-dependent cancers, front-line treatment options include surgery and therapies that target hormone dependance. These therapies are effective initially but fail in tumors that recur, develop resistance or present at an advanced stage. Consequently, new therapeutic avenues are urgently needed. Increasing evidence implicates epigenetic modulators in tumor initiation, progression and therapeutic response, making them attractive biomarkers for patient stratification and targets for intervention. Over the past two decades, the discovery and development of small-molecule inhibitors directed against key epigenetic regulators have accelerated. This review provides a comprehensive overview of the major epigenetic targets, the inhibitors developed against them and the clinical trials currently underway in endocrine-related cancers. While epigenetic agents have shown limited benefits as monotherapies, their use in combination regimens is emerging as a strategy to overcome resistance and enhance the efficacy of existing treatments. We summarize the current landscape of combination trials, highlight early signs of clinical activity and discuss the opportunities and challenges inherent in integrating epigenetic drugs into the management of advanced endocrine-related cancers.
在激素依赖性癌症中，一线治疗方案包括手术及针对激素依赖性的疗法。这些疗法在初期有效，但对复发、产生耐药性或晚期肿瘤则效果不佳。因此，亟需探索新的治疗途径。越来越多的证据表明，表观遗传调控因子在肿瘤发生、进展及治疗反应中发挥重要作用，使其成为患者分层和干预靶点的理想生物标志物。过去二十年间，针对关键表观遗传调控因子的小分子抑制剂的研发进程显著加快。本综述系统概述了主要表观遗传靶点、针对这些靶点开发的抑制剂以及目前在内分泌相关癌症中开展的临床试验。虽然表观遗传药物单药治疗获益有限，但其在联合方案中的应用正逐渐成为克服耐药性和增强现有治疗效果的策略。我们总结了当前联合治疗的试验进展，重点分析了临床活性的早期迹象，并探讨了将表观遗传药物纳入晚期内分泌相关癌症治疗体系所面临的机遇与挑战。
Epigenetic Therapies in Endocrine-Related Cancers: Past Insights and Clinical Progress
肿瘤(癌症)患者之家