Targeting the translational machinery as a novel treatment strategy for hematologic malignancies

• Published in: Blood Vol. 115; no. 11; pp. 2127 - 2135
• Main Authors: Hagner, Patrick R., Schneider, Abraham, Gartenhaus, Ronald B.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 18-03-2010; Americain Society of Hematology; American Society of Hematology
• Series: Review Article
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Eukaryotic Initiation Factor-4F - metabolism; Hematologic and hematopoietic diseases; Hematologic Neoplasms - drug therapy; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Medical sciences; Protein Biosynthesis - drug effects; Protein-Serine-Threonine Kinases - metabolism; Review; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; TOR Serine-Threonine Kinases; Malignant hemopathy; Treatment; Targeting; Hematology; Genetic translation; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-09-220020

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.