FLT3抑制剂及逆转AML耐药的新疗法：一份更新的综述。
FLT3 inhibitors and novel therapeutic strategies to reverse AML resistance: an updated comprehensive review.
发表日期：2023 Sep 15
作者：
Amal Kamal Abdel-Aziz, Eman M E Dokla, Mona Kamal Saadeldin
来源：
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
摘要：
FMS样酪氨酸激酶3(FLT3)的突变在近30%的急性髓系白血病(AML)患者中发生。尽管FLT3抑制剂最初在治疗突变型FLT3的AML患者中显示出一定的临床疗效，但许多接受治疗的患者最终会复发。本综述对FLT3靶向疗法的潜力和挑战进行了批判性讨论，并阐明了其药物相互作用以及潜在生物标志物。此外，我们重点研究了FLT3内源性串联重复(FLT3-ITD)型AML对FLT3抑制剂的耐药性的分子机制，以及逆转耐药性的新的治疗策略。值得注意的是，动态的克隆选择和演化模式对于FLT3-ITD型AML对FLT3抑制剂的耐药性起到了贡献。正在进行的临床前研究和临床试验积极致力于设计合理的“个体化”或“针对患者”的联合治疗方案，以有效地治疗FLT3突变型AML的患者。版权所有© 2023 Elsevier B.V. 保留所有权利。
FMS-like tyrosine kinase 3 (FLT3) mutations occur in almost 30% of acute myeloid leukemia (AML) patients. Despite the initial clinical efficacy of FLT3 inhibitors, many treated AML patients with mutated FLT3 eventually relapse. This review critically discusses the potential and challenges of FLT3-targeted therapies and sheds light on their drug interactions as well as potential biomarkers. Furthermore, we focus on the molecular mechanisms underlying the resistance of FLT3 internal tandem duplication (FLT3-ITD) AMLs to FLT3 inhibitors alongside novel therapeutic strategies to reverse resistance. Notably, dynamic heterogeneous patterns of clonal selection and evolution contribute to the resistance of FLT3-ITD AMLs to FLT3 inhibitors. Ongoing preclinical research and clinical trials are actively directed towards devising rational "personalized" or "patient-tailored" combinatorial therapeutic regimens to effectively treat patients with FLT3 mutated AML.Copyright © 2023 Elsevier B.V. All rights reserved.