Department of Medical Oncology/Hematologic Neoplasia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Oncogene. 2010 Sep 16;29(37):5120-34. doi: 10.1038/onc.2010.273. Epub 2010 Jul 12.
Mutant Fms-Like Tyrosine kinase-3 (FLT3), which is expressed in the leukemic cells of a subpopulation of acute myeloid leukemia (AML) patients, represents an attractive target for the therapy of AML. There are several FLT3 inhibitors presently in clinical trials with sufficient efficacy and toxicity features to warrant further testing in combination with standard therapies. However, the transient and partial responses observed in AML patients treated with FLT3 inhibitors, coupled with the discovery of drug-resistant leukemic blast cells in AML patients, have made resistance to FLT3 inhibitors a growing concern. In this study, we provide an overview of the role of mutant FLT3 in AML, FLT3 inhibitors under clinical and preclinical investigation, mechanisms of resistance to FLT3 inhibitors, and possible therapeutic approaches to overcoming this resistance.
突变型 Fms 样酪氨酸激酶-3（FLT3）在急性髓系白血病（AML）患者亚群的白血病细胞中表达，是 AML 治疗的一个有吸引力的靶点。目前有几种 FLT3 抑制剂正在临床试验中，其疗效和毒性特征足以证明与标准疗法联合进一步测试是合理的。然而，在接受 FLT3 抑制剂治疗的 AML 患者中观察到的短暂和部分缓解，以及在 AML 患者中发现对 FLT3 抑制剂耐药的白血病母细胞，使得对 FLT3 抑制剂的耐药性成为一个日益严重的问题。在这项研究中，我们概述了突变型 FLT3 在 AML 中的作用、临床和临床前研究中的 FLT3 抑制剂、对 FLT3 抑制剂的耐药机制，以及克服这种耐药性的可能治疗方法。
