Wiernik Peter H
Cancer Research Foundation, Chappaqua, NY 10514, USA.
Clin Adv Hematol Oncol. 2010 Jun;8(6):429-36, 444.
The fms-like receptor tyrosine kinase-3 (FLT3), which is important for the normal development of hematopoietic stem cells and cells of the immune system, is frequently mutated in patients with acute myeloid leukemia (AML). FLT3 is, therefore, a potential therapeutic target in AML. Recently, FLT3 inhibitors have shown therapeutic activity in AML patients with FLT3 mutations. Sorafenib and sunitinib were the first FLT3 inhibitors to be studied in the clinic and have the most clinically relevant data. Limited data are available for midostaurin (PKC412), lestaurtinib (CEP-701), tandutinib (MLN518), AC220, and KW-2449. It is likely that optimal application of these agents will involve combinations of inhibitors and combinations of inhibitors and chemotherapy, potentially with a mammalian target of rapamycin inhibitor such as everolimus or temsirolimus. This review discusses the theoretical rationale for the use of these agents and summarizes the relevant clinical data.
Fms样受体酪氨酸激酶3（FLT3）对造血干细胞和免疫系统细胞的正常发育至关重要，在急性髓系白血病（AML）患者中经常发生突变。因此，FLT3是AML潜在的治疗靶点。最近，FLT3抑制剂在携带FLT3突变的AML患者中显示出治疗活性。索拉非尼和舒尼替尼是首批进入临床研究的FLT3抑制剂，拥有最具临床相关性的数据。关于米哚妥林（PKC412）、来他替尼（CEP-701）、坦度替尼（MLN518）、AC220和KW-2449的可用数据有限。这些药物的最佳应用可能涉及抑制剂联合、抑制剂与化疗联合，可能还会联合使用哺乳动物雷帕霉素靶蛋白抑制剂，如依维莫司或替西罗莫司。本综述讨论了使用这些药物的理论依据，并总结了相关临床数据。
