BH3 mimetics and multi-kinase inhibition in AML

摘要

In this issue of Blood, Rahmani et al show in preclinical studies that the combination of the multi-kinase inhibitor sorafenib with the BH3 mimetic obatoclax results in enhanced antileukemic effects compared with the effects of each agent alone.1 This work has important clinical implications because it describes a novel approach to overcome acute myeloid leukemia (AML) cell resistance by combining agents that are currently being investigated in trials as single agents. Despite recent advances on our understanding of mechanism and cellular pathways that promote proliferation and survival of leukemia cells, there is a desperate need for the design and development of innovative therapeutic approaches for the treatment of patients with AML. Sorafenib is a multi-kinase inhibitor, which targets and inhibits several tyrosine and serine-threonine kinases, including FLT3, RAF, VEGFR, PDGF, and c-kit. This agent has shown substantial clinical efficacy and is currently approved by the US Food and Drug Administration for the treatment of advanced hepatocellular and renal cell carcinoma.