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 opportunities 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.
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| http://dx.doi.org/10.1016/j.critrevonc.2023.104139 | DOI Listing |
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