Smith Catherine C, Shah Neil P
From the Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Am Soc Clin Oncol Educ Book. 2013:313-8. doi: 10.14694/EdBook_AM.2013.33.313.
Multiple small molecule kinase inhibitors are currently undergoing development for the treatment of acute myeloid leukemia (AML). Recently, selective and potent FLT3 inhibitors such as AC220 (quizartinib) have proven clinically effective in patients with AML with FLT3 internal tandem duplication (ITD) mutations, but inhibitors of other pathologically activated kinases in AML such as c-KIT and JAK2 have achieved less clinical success. Other classes of inhibitors currently undergoing clinical development target mediators of downstream signaling pathways such as mTOR and MEK or cell cycle machinery such as aurora kinases, PLK1, or cyclin-dependent kinases. Other than FLT3 inhibitors, most inhibitors have achieved only rare bone marrow responses, and kinase inhibitor therapy in AML remains investigational. Continuing efforts to develop kinase inhibitors for the treatment of AML will require careful selection of patients for clinical trials, translational studies to characterize responders, and investigation of combination therapy that may be capable of improving response rates and duration.
目前有多种小分子激酶抑制剂正在研发用于治疗急性髓系白血病（AML）。最近，选择性强效FLT3抑制剂如AC220（quizartinib）已在伴有FLT3内部串联重复（ITD）突变的AML患者中证明具有临床疗效，但AML中其他病理激活激酶如c-KIT和JAK2的抑制剂在临床上取得的成功较少。目前正在进行临床开发的其他类抑制剂靶向下游信号通路的介质如mTOR和MEK或细胞周期机制如极光激酶、PLK1或细胞周期蛋白依赖性激酶。除FLT3抑制剂外，大多数抑制剂仅获得罕见的骨髓反应，AML中的激酶抑制剂治疗仍处于研究阶段。继续努力开发用于治疗AML的激酶抑制剂将需要仔细选择临床试验患者、进行转化研究以表征反应者，并研究可能能够提高反应率和持续时间的联合治疗。
