Zhao Guangjie, Wang Qian, Li Shuang, Wang Xiaoqin
Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
Front Oncol. 2021 Sep 28;11:706030. doi: 10.3389/fonc.2021.706030. eCollection 2021.
The nucleoside analogs decitabine (5-AZA-dC) and azacitidine (5-AZA) have been developed as targeted therapies to reverse DNA methylation in different cancer types, and they significantly improve the survival of patients who are not suitable for traditional intensive chemotherapies or other treatment regimens. However, approximately 50% of patients have a response to hypomethylating agents (HMAs), and many patients have no response originally or in the process of treatment. Even though new combination regimens have been tested to overcome the resistance to 5-AZA-dC or 5-AZA, only a small proportion of patients benefited from these strategies, and the outcome was very poor. However, the mechanisms of the resistance remain unknown. Some studies only partially described management after failure and the mechanisms of resistance. Herein, we will review the clinical and molecular signatures of the HMA response, alternative treatment after failure, and the causes of resistance in hematological malignancies.
核苷类似物地西他滨（5-氮杂-2'-脱氧胞苷）和阿扎胞苷（5-氮杂胞苷）已被开发为靶向疗法，用于逆转不同癌症类型中的DNA甲基化，并且它们显著提高了不适合传统强化化疗或其他治疗方案的患者的生存率。然而，大约50%的患者对低甲基化剂（HMAs）有反应，许多患者最初或在治疗过程中没有反应。尽管已经测试了新的联合方案以克服对5-氮杂-2'-脱氧胞苷或5-氮杂胞苷的耐药性，但只有一小部分患者从这些策略中受益，且结果非常差。然而，耐药机制仍然未知。一些研究仅部分描述了失败后的处理方法和耐药机制。在此，我们将综述血液系统恶性肿瘤中HMA反应的临床和分子特征、失败后的替代治疗以及耐药原因。
