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Mechanisms of Resistance to Small Molecules in Acute Myeloid Leukemia
Tonio Johannes Lukas Lang1, Frederik Damm1,2, Lars Bullinger1,2
1Department of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353 Berlin, Germany.
Abstract:
In recent years, great progress has been made in the therapy of AML by targeting cellular processes associated with specific molecular features of the disease. Various small molecules inhibiting FLT3, IDH1/IDH2, and BCL2 have already gained approval from the respective authorities and are essential parts of personalized therapeutic regimens in modern therapy of AML. Unfortunately, primary and secondary resistance to these inhibitors is a frequent problem. Here, we comprehensively review the current state of knowledge regarding molecular processes involved in primary and secondary resistance to these agents, covering both genetic and nongenetic mechanisms. In addition, we introduce concepts and strategies for how these resistance mechanisms might be overcome.
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