Exploiting the mammalian target of rapamycin pathway in... : Current Opinion in Hematology (original) (raw)

Myeloid disease: Edited by Martin S. Tallman

Exploiting the mammalian target of rapamycin pathway in hematologic malignancies

Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University Medical School and Lakeside Veterans Affairs Medical Center, Chicago, Illinois, USA

Correspondence to Leonidas C. Platanias, Robert H. Lurie Comprehensive Cancer Center, 303 East Superior Street, Lurie 3-107, Chicago, IL 60611, USA Tel: +1 312 503 4267; fax: +1 312 908 1372; e-mail: [email protected]

Abstract

Purpose of review

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.

Recent findings

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.

Summary

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.