Targeting the translational machinery as a novel treatment strategy for hematologic malignancies.
The dysregulation of protein synthesis evident in the transformed phenotype has opened up a burgeoning field of research in cancer biology. Translation initiation has recently been shown to be a common downstream target of signal transduction pathways deregulated in cancer and initiated by mutated/overexpressed oncogenes and tumor suppressors. The overexpression and/or activation of proteins involved in translation initiation such as eIF4E, mTOR, and eIF4G have been shown to induce a malignant phenotype. Therefore, understanding the mechanisms that control protein synthesis is emerging as an exciting new research area with significant potential for developing innovative therapies. This review highlights molecules that are activated or dysregulated in hematologic malignancies, and promotes the transformed phenotype through the deregulation of protein synthesis. Targeting these proteins with small molecule inhibitors may constitute a novel therapeutic approach in the treatment of cancer.
Hagner
Patrick R
PR
Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Schneider
Abraham
A
Gartenhaus
Ronald B
RB
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D039562:Eukaryotic Initiation Factor-4F; D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases