Abstract
Reflecting its critical role in integrating cell growth and division with the cellular nutritional environment, the mammalian target of rapamycin *(mTOR) is a highly conserved downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B) signaling pathway. mTOR activates both the 40S ribosomal protein S6 kinase (p70s6k) and the eukaryotic initiation factor 4E-binding protein-1. As a consequence of inhibiting its downstream messengers, mTOR inhibitors prevent cyclindependent kinase (CDK) activation, inhibit retinoblastoma protein phosphorylation, and accelerate the turnover of cyclin D1, leading to a deficiency of active CDK4/cyclin D1 complexes, all of which may help cause GI phase arrest. Constitutive activation of the PI3K/Akt kinases occur in human leukemias. FLT3, VEGF, and BCR-ABL mediate their activities via mTOR. New rapamycin analogs including CCI- 779, RAD001, and AP23573, are entering clinical studies for patients with hematologic malignancies.
Keywords: mTOR, leukemia, phosphatidylinositol 3' kinase, AKT, CCI-779, RAD001, AP23573
Current Molecular Medicine
Title: Mammalian Target of Rapamycin as a Therapeutic Target in Leukemia
Volume: 5 Issue: 7
Author(s): Francis J. Giles and Maher Albitar
Affiliation:
Keywords: mTOR, leukemia, phosphatidylinositol 3' kinase, AKT, CCI-779, RAD001, AP23573
Abstract: Reflecting its critical role in integrating cell growth and division with the cellular nutritional environment, the mammalian target of rapamycin *(mTOR) is a highly conserved downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B) signaling pathway. mTOR activates both the 40S ribosomal protein S6 kinase (p70s6k) and the eukaryotic initiation factor 4E-binding protein-1. As a consequence of inhibiting its downstream messengers, mTOR inhibitors prevent cyclindependent kinase (CDK) activation, inhibit retinoblastoma protein phosphorylation, and accelerate the turnover of cyclin D1, leading to a deficiency of active CDK4/cyclin D1 complexes, all of which may help cause GI phase arrest. Constitutive activation of the PI3K/Akt kinases occur in human leukemias. FLT3, VEGF, and BCR-ABL mediate their activities via mTOR. New rapamycin analogs including CCI- 779, RAD001, and AP23573, are entering clinical studies for patients with hematologic malignancies.
Export Options
About this article
Cite this article as:
Giles J. Francis and Albitar Maher, Mammalian Target of Rapamycin as a Therapeutic Target in Leukemia, Current Molecular Medicine 2005; 5 (7) . https://dx.doi.org/10.2174/156652405774641034
DOI https://dx.doi.org/10.2174/156652405774641034 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
- 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
-
Review of PI3K/mTOR Inhibitors Entering Clinical Trials to Treat Triple Negative Breast Cancers
Recent Patents on Anti-Cancer Drug Discovery Histone Deacetylase Inhibition: A Differentiation Therapy for Cultured Primary Hepatocytes?
Current Enzyme Inhibition Erratum
Current Cancer Drug Targets Incorporation of Targeted Agents in the Management of Patients with Advanced Gastric Cancer
Current Medicinal Chemistry AKT Signaling in Regulating Angiogenesis
Current Cancer Drug Targets Recent Advances in Computer-Assisted Structure-Based Identification and Design of Histone Deacetylases Inhibitors
Current Topics in Medicinal Chemistry Cellular Mechanisms of Bypass Vein Graft Arterialization and Approaches to Attenuate Graft Remodeling
Vascular Disease Prevention (Discontinued) Anal Cancer: Focus on HIV-Positive Patients in the HAART Era
Current HIV Research Antiproliferative Strategies for the Treatment of Vascular Proliferative Disease
Current Vascular Pharmacology Pharmacological Activation of p53 in Cancer Cells
Current Pharmaceutical Design The Prodigiosins: A New Family of Anticancer Drugs
Current Cancer Drug Targets A Family of Pleiotropically Acting MicroRNAs in Cancer Progression, miR-200: Potential Cancer Therapeutic Targets
Current Pharmaceutical Design Promising Activity of Mammalian Target of Rapamycin Inhibitors in Hematologic Malignancies Therapy
Current Signal Transduction Therapy Inhibition of Cyclin-Dependent Kinases - A Review of the Recent Patent Literature
Recent Patents on Anti-Cancer Drug Discovery Gankyrin Oncoprotein: Structure, Function, and Involvement in Cancer
Current Chemical Biology FOXO Transcription Factors and their Role in Disorders of the Female Reproductive Tract
Current Drug Targets Standards and Novel Therapeutic Options in the Treatment of Patients with Soft Tissue Sarcoma
Reviews on Recent Clinical Trials Application and Interpretation of Genome-Wide Association (GWA) Studies for Informing Pharmacogenomic Research - Examples from the Field of Age-Related Macular Degeneration
Current Molecular Medicine Receptor Tyrosine Kinases as Target for Anti-Cancer Therapy
Current Pharmaceutical Design Glioma: Tryptophan Catabolite and Melatoninergic Pathways Link microRNA, 14-3- 3, Chromosome 4q35, Epigenetic Processes and other Glioma Biochemical Changes
Current Pharmaceutical Design