Rapid advances in the field of epigenetics have facilitated the development of novel therapeutics targeting epigenetic mechanisms that are hijacked by cancer cells to support tumour growth and progression. Several epigenetic agents have been approved by the FDA for the treatment of cancer; however, the efficacy of these drugs is dependent on the underlying biology and drivers of the disease, with inherent differences between solid tumours and haematological malignancies. The efficacy of epigenetic drugs as single agents remains limited across most cancer types, which has spurred the clinical development of combination therapies, with the hope of attaining synergistic activity and/or overcoming treatment resistance. In this Review we discuss clinical advances that have been achieved with the use of epigenetic agents in combination with chemotherapies, immunotherapies or other targeted agents, including epigenetic–epigenetic combinations, as well as limitations and challenges associated with these combinatorial strategies. So far, the success of combination therapies targeting epigenetic mechanisms has generally been confined to haematological malignancies, with limited efficacy observed in patients with solid tumours. Nevertheless, this Review captures the field of epigenetic combination therapies across the spectra of haematology and oncology, highlighting opportunities for precision therapy to effectively harness the potential of epigenetic agents and produce meaningful improvements in clinical outcomes.

表观遗传学领域的快速发展促进了针对被癌细胞劫持以支持肿瘤生长和进展的表观遗传机制的新型疗法的开发。几种表观遗传学药物已被 FDA 批准用于治疗癌症;然而，这些药物的疗效取决于潜在的生物学和疾病的驱动因素，实体瘤和血液系统恶性肿瘤之间存在内在差异。在大多数癌症类型中，表观遗传药物作为单一药物的疗效仍然有限，这刺激了联合疗法的临床开发，以期获得协同活性和/或克服治疗耐药性。在本综述中，我们讨论了表观遗传学试剂与化疗、免疫疗法或其他靶向药物（包括表观遗传学-表观遗传学组合）联合使用所取得的临床进展，以及与这些组合策略相关的局限性和挑战。到目前为止，针对表观遗传机制的联合疗法的成功通常局限于血液系统恶性肿瘤，在实体瘤患者中观察到的疗效有限。尽管如此，本综述涵盖了血液学和肿瘤学领域的表观遗传学联合疗法，强调了精准治疗的机会，以有效利用表观遗传学药物的潜力并对临床结果产生有意义的改善。