Hosono Naoko
Department of Hematology and Oncology, University of Fukui.
Rinsho Ketsueki. 2019;60(9):1108-1119. doi: 10.11406/rinketsu.60.1108.
Conventional chemotherapy with cytarabine and anthracycline (often referred to as "7+3") has been used for many years in the treatment of acute myeloid leukemia (AML). Despite meaningful advances in areas of supportive care and transplantation, little progress has been made in developing new chemotherapy options. In 2018, The Food and Drug Administration (FDA) of the US approved several novel agents for AML treatment as follows: ivosidenib, an inhibitor of isocitrate dehydrogenase-1; venetoclax, a potent inhibitor of bcl2; and glasdegib, an inhibitor of hedgehog signaling pathway. Moreover, clinical trials of alvocidib (flavopiridol), an inhibitor of the CDK9, pevonedistat, an inhibitor of NEDD8, and APR-246, a reactivator of mutant p53, are in progress. These agents will either be incorporated into the conventional 7+3 regimen or combined with hypomethylating agents to improve the outcome of AML therapy, and the results will guide the next stage of precision medicine in the treatment of AML.
阿糖胞苷和蒽环类药物的传统化疗（常被称为“7+3”方案）已用于治疗急性髓系白血病（AML）多年。尽管在支持治疗和移植领域取得了显著进展，但在开发新的化疗方案方面进展甚微。2018年，美国食品药品监督管理局（FDA）批准了几种用于AML治疗的新型药物，如下所示：异柠檬酸脱氢酶-1抑制剂艾伏尼布；强效bcl2抑制剂维奈克拉；以及刺猬信号通路抑制剂格拉斯吉布。此外，细胞周期蛋白依赖性激酶9（CDK9）抑制剂阿沃西地布（黄酮哌啶醇）、NEDD8抑制剂pevonedistat和突变型p53再激活剂APR-246的临床试验正在进行中。这些药物要么会被纳入传统的“7+3”方案，要么与去甲基化药物联合使用，以改善AML治疗的效果，其结果将为AML治疗精准医学的下一阶段提供指导。
