Advancements in targeted therapies for acute myeloid leukemia.

For decades, the only therapeutic option for acute myeloid leukemia (AML) had been intensive combination chemotherapy. In recent years, understanding of the molecular mechanisms underlying myeloid oncogenesis has grown immensely and has led to the development of multiple effective small molecule inhibitors of aberrant cellular signaling. This review highlights the major AML mutational pathways currently being targeted with precision therapies: the receptor tyrosine kinase FLT3, the citric acid cycle enzymes IDH1 and IDH2, and the transcription-regulating KMT2A and NPM1 genes. We review the major clinical trials evaluating the safety and efficacy of agents targeting these pathways, as well as ongoing and upcoming studies of novel and combination therapies for these molecular subsets of AML.