The understanding of the molecular pathobiology of acute myeloid leukemia (AML) has spurred the identification of therapeutic targets and the development of corresponding novel targeted therapies. Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in AML]); and CPX-351 (encapsulated liposomal 5:1 molar ratio of cytarabine and daunorubicin), and glasdegib (hedgehog inhibitor). Other targeted therapies (menin inhibitors, CD123 antibody-drug conjugates) are showing promising results. To achieve optimal results in such a rare and heterogeneous entity as AML requires expertise, familiarity with this rare cancer, and the access to, and delivery of disparate therapies under rigorous supportive care conditions. In this review, we update the standard-of-care and investigational therapies and outline promising current and future research directions.
对急性髓系白血病（AML）分子病理生物学的认识促进了治疗靶点的识别及相应新型靶向疗法的开发。自2017年以来，已有十二种药物获批用于特定AML亚型的治疗：BCL2抑制剂维奈克拉；CD33抗体药物偶联物吉妥珠单抗奥佐米星；三种FLT3抑制剂（米哚妥林、吉瑞替尼、奎扎替尼）；三种IDH抑制剂（艾伏尼布和奥拉妥替尼靶向IDH1突变，恩西地平靶向IDH2突变）；两种口服低甲基化剂（口服低吸收阿扎胞苷；完全吸收型地西他滨-cedazuridine复方制剂[后者获批作为骨髓增生异常综合征和慢性粒单核细胞白血病中胃肠外低甲基化剂的替代方案，但常被用于AML]）；以及CPX-351（阿糖胞苷与柔红霉素以5:1摩尔比封装脂质体）和格拉吉布（Hedgehog信号通路抑制剂）。其他靶向疗法（menin抑制剂、CD123抗体药物偶联物）亦展现出积极疗效。要在AML这种罕见且高度异质性的疾病中获得最佳疗效，需要专业医学知识、对该罕见癌症的深刻理解，以及在严格支持治疗条件下获取并实施多样化治疗的能力。本文综述将更新当前标准治疗方案与探索性疗法，并概述当前及未来具有前景的研究方向。
Current status and research directions in acute myeloid leukemia
肿瘤(癌症)患者之家