Acute myeloid leukemia: potential for new therapeutic approaches targeting mRNA translation pathways

Despite advances in molecular research related to acute myeloid leukemia (AML) and a better understanding of the mechanisms of leukemogenesis and pathophysiology of the disease, the pharmacological agents used in the treatment of AML have remained essentially unchanged for the last three decades. Advances in the clinical management of AML patients have been achieved by defining better molecular prognostic markers, but there remains a need for new targeted drugs that disrupt non-overlapping pathways in leukemia cells. The mTOR cellular cascade is critical for cell metabolism, growth, proliferation and survival. Extensive preclinical work suggests that targeting mTOR may provide a powerful approach to block AML precursor cells, while other findings suggest enhanced antileukemic effects by combining mTOR inhibitors with traditional chemotherapy. Such combinations may increase antileukemic responses further, offering unique ways to overcome leukemic cell resistance and to eliminate primitive leukemic precursors.