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
-
Apoptosis: Its Functions and Control in the Ocular Lens
Current Molecular Medicine Environmental Risk Assessment of Replication Competent Viral Vectors Applied in Clinical Trials: Potential Effects of Inserted Sequences
Current Gene Therapy Immunosuppressive Drugs in HIV Disease
Current Topics in Medicinal Chemistry Gene Delivery Strategies Targeting Stable Atheromatous Plaque
Current Pharmaceutical Design Power from the Garden: Plant Compounds as Inhibitors of the Hallmarks of Cancer
Current Medicinal Chemistry Identification and Preclinical Evaluation of SC144, a Novel Pyrroloquinoxaline Derivative with Broad-Spectrum Anticancer Activity
Mini-Reviews in Medicinal Chemistry Bioenergetics and Mitochondrial Dysfunction in Aging: Recent Insights for a Therapeutical Approach
Current Pharmaceutical Design Aptamer-Based Targeted Drug Delivery Systems: Current Potential and Challenges
Current Medicinal Chemistry The ‘Other’ Telomerase Inhibitors: Non-G-Quadruplex Interactive Agent, Non-Antisense, Non-Reverse Transcriptase Telomerase Inhibitors
Current Medicinal Chemistry - Anti-Cancer Agents Structure and Function of the Epstein-Barr Virus Transcription Factor, EBNA 3C
Current Protein & Peptide Science The Polyhedric Abl Kinases and their Pharmacologic Inhibitors
Current Enzyme Inhibition Retinoblastoma Regulatory Pathway in Lung Cancer
Current Molecular Medicine Advances in Ocular Iontophoresis Research
Recent Patents on Nanomedicine Genetics, Gene Expression, and Targeted Therapies in Chronic Lymphocytic Leukemia
Current Drug Targets Deubiquitinating Enzymes as Therapeutic Targets in Cancer
Current Pharmaceutical Design Combining Oncolytic Virotherapy and Cytotoxic Therapies to Fight Cancer
Current Pharmaceutical Design MicroRNA and Bone Tumor: To Up Date
Current Signal Transduction Therapy Fibroblast Growth Factors, Fibroblast Growth Factor Receptors, Diseases, and Drugs
Recent Patents on Cardiovascular Drug Discovery Manipulating the Ability of Substituted Titanocene Derivatives to Induce Apoptosis in Castrate-Resistant Prostate Cancer Cells
Letters in Drug Design & Discovery Platelets in Alzheimer’s Disease-Associated Cellular Senescence and Inflammation
Current Pharmaceutical Design