Exploiting the mammalian target of rapamycin pathway in hematologic malignancies

Abstract

This review critically assesses recent research advances in elucidating the role of the mammalian target of rapamycin pathway in the pathogenesis of hematologic malignancies and the potential of targeting this signaling pathway to treat such malignancies. Mammalian target of rapamycin is a highly conserved serine/threonine protein kinase that controls initiation of mRNA translation, cell cycle progression, and cellular proliferation. Recent dramatic advances in research into cellular signaling by mammalian target of rapamycin and its effectors, and better understanding of aberrant activation of mammalian target of rapamycin pathways in hematologic malignancies have stimulated considerable interest in the clinical development of inhibitors that target this pathway. Numerous clinical trials using mammalian target of rapamycin inhibitors are ongoing in various hematologic malignancies. Such trials are direct extensions of preclinical work establishing that inhibition of this pathway blocks cell proliferation and/or induces apoptotic cell death, both in vitro and in vivo. The role of the mammalian target of rapamycin pathway in hematologic malignancies is of considerable interest with major clinical/translational relevance. Here, our understanding of the functional roles of the mammalian target of rapamycin pathway and its deregulation in hematologic malignancies are summarized and resulting clinical/translational efforts discussed.