Abstract
Since its first description nearly a decade ago, mammalian target of rapamycin (mTOR) has emerged as a critical regulator of cell size and growth in normal and neoplastic conditions. Many cancers rely on mTOR pathway members for their survival, and these proteins thus form attractive targets with wide potential therapeutic indices. Understanding the role of mTOR in lymphomagenesis is complicated by the intricacy of upstream and downstream components as well as potential differences due to the inherent heterogeneity of lymphoma subtypes. Nevertheless, significant data supports a central role of mTOR pathway in lymphoma. Several lymphoma subtypes harbor PTEN deletions, Akt overexpression, or increased eIF4E. Rapamycin is the prototypical mTOR inhibitor, and has clear anti-tumor effects in many lymphoma preclinical models. Newer rapamycin analogs, including the prodrugs temsirolimus and everolimus, and the non prodrug AP23573, are in clinical trials with preliminary, but promising, activity in hematologic malignancies. The limited treatment options for many patients with relapsed lymphomas coupled with the encouraging activity of mTOR inhibitors warrant ongoing attention and clinical development of these agents.
Keywords: Mammalian TOR (mTOR), Rapamycin, Lymphoma, Lymphomagenesis, PI3 kinase, Akt
Letters in Drug Design & Discovery
Title: mTOR Inhibition in Lymphoma: A Rational and Promising Strategy
Volume: 4 Issue: 3
Author(s): Sonali M. Smith and Koen van Besien
Affiliation:
Keywords: Mammalian TOR (mTOR), Rapamycin, Lymphoma, Lymphomagenesis, PI3 kinase, Akt
Abstract: Since its first description nearly a decade ago, mammalian target of rapamycin (mTOR) has emerged as a critical regulator of cell size and growth in normal and neoplastic conditions. Many cancers rely on mTOR pathway members for their survival, and these proteins thus form attractive targets with wide potential therapeutic indices. Understanding the role of mTOR in lymphomagenesis is complicated by the intricacy of upstream and downstream components as well as potential differences due to the inherent heterogeneity of lymphoma subtypes. Nevertheless, significant data supports a central role of mTOR pathway in lymphoma. Several lymphoma subtypes harbor PTEN deletions, Akt overexpression, or increased eIF4E. Rapamycin is the prototypical mTOR inhibitor, and has clear anti-tumor effects in many lymphoma preclinical models. Newer rapamycin analogs, including the prodrugs temsirolimus and everolimus, and the non prodrug AP23573, are in clinical trials with preliminary, but promising, activity in hematologic malignancies. The limited treatment options for many patients with relapsed lymphomas coupled with the encouraging activity of mTOR inhibitors warrant ongoing attention and clinical development of these agents.
Export Options
About this article
Cite this article as:
Smith M. Sonali and van Besien Koen, mTOR Inhibition in Lymphoma: A Rational and Promising Strategy, Letters in Drug Design & Discovery 2007; 4 (3) . https://dx.doi.org/10.2174/157018007780077435
DOI https://dx.doi.org/10.2174/157018007780077435 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Liposomal-All-trans-Retinoic Acid in the Treatment of Acute Promyelocytic Leukemia
Current Cancer Therapy Reviews An Update on Autoinflammatory Diseases
Current Medicinal Chemistry 99mTechnetium- or Cy7-Labeled Fab(Tocilizumab) as Potential Multiple Myeloma Imaging Agents
Anti-Cancer Agents in Medicinal Chemistry Transfusion-related Acute Lung Injury: An Overview
Current Pharmaceutical Design Stem Cells, Cancer, Liver, and Liver Cancer Stem Cells: Finding a Way Out of the Labyrinth...
Current Cancer Drug Targets Cancer/Testis Antigens Trigger Epithelial-Mesenchymal Transition and Genesis of Cancer Stem-Like Cells
Current Pharmaceutical Design Thiopurine Immunomodulators in Ulcerative Colitis: Moving Forward with Current Evidence
Current Drug Targets Tipping the Balance Between Life and Death: Targeting Histone Acetylation for Cancer Therapy
Drug Delivery Letters Biological Basis of Novel Therapies for Myelodysplastic Syndrome
Current Cancer Therapy Reviews Iron Chelators: Development of Novel Compounds with High and Selective Anti-Tumour Activity
Current Drug Delivery Targeting the Expression of Anti-Apoptotic Proteins by Antisense Oligonucleotides
Current Drug Targets Polysulfated/Sulfonated Compounds for the Development of Drugs at the Crossroad of Viral Infection and Oncogenesis
Current Pharmaceutical Design Newer Avenues for the Treatment of Leptomeningeal Carcinomatosis
Central Nervous System Agents in Medicinal Chemistry Chemopreventive and Anti-leukemic Effects of Ethanol Extracts of Moringa oleifera Leaves on Wistar Rats Bearing Benzene Induced Leukemia
Current Pharmaceutical Biotechnology Chemistry and Pharmacology of Angiotensin-Converting Enzyme Inhibitors
Current Pharmaceutical Design Editorial (Thematic Issue: The Effects of Anticancer Agents on Cell Apoptosis and on the Expression of Cancer - Related Genes)
Anti-Cancer Agents in Medicinal Chemistry microRNA Biogenesis Pathway as a Therapeutic Target for Human Disease and Cancer
Current Pharmaceutical Design Epigenetic Modifications as Therapeutic Targets
Current Drug Targets Safety of Gene Therapy: New Insights to a Puzzling Case
Current Gene Therapy The Role of EGFR Tyrosine Kinase Inhibitors in the First-Line Treatment of Advanced Non Small Cell Lung Cancer Patients Harboring EGFR Mutation
Current Medicinal Chemistry