Role of Biomarkers in FLT3 AML
CANCERS(2022)
摘要
Simple Summary: Genetically heterogeneous disorder acute myeloid leukemia (AML) is marked by recurring mutations in FLT3. Current FLT3 inhibitors and other emerging inhibitors have helped in the improvement of the quality of standard of care therapies; however, the overall survival of the patients remains static. This is due to numerous mutations in FLT3, which causes resistance against these FLT3 inhibitors. For effective treatment of AML patients, alternative approaches are required to overcome this resistance. Here, we will summarize the biomarkers for FLT3 inhibitors in AML, as well as the alternative measures to overcome resistance to the current therapies. Acute myeloid leukemia is a disease characterized by uncontrolled proliferation of clonal myeloid blast cells that are incapable of maturation to leukocytes. AML is the most common leukemia in adults and remains a highly fatal disease with a five-year survival rate of 24%. More than 50% of AML patients have mutations in the FLT3 gene, rendering FLT3 an attractive target for smallmolecule inhibition. Currently, there are several FLT3 inhibitors in the clinic, and others remain in clinical trials. However, these inhibitors face challenges due to lack of efficacy against several FLT3 mutants. Therefore, the identification of biomarkers is vital to stratify AML patients and target AML patient population with a particular FLT3 mutation. Additionally, there is an unmet need to identify alternative approaches to combat the resistance to FLT3 inhibitors. Here, we summarize the current knowledge on the utilization of diagnostic, prognostic, predictive, and pharmacodynamic biomarkers for FLT3-mutated AML. The resistance mechanisms to various FLT3 inhibitors and alternative approaches to combat this resistance are also discussed and presented.
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关键词
acute myeloid leukemia,FLT3 inhibitors,FLT3-ITD,FLT3-TKD,biomarkers,resistance
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