Abstract
The PI3K/Akt signaling network regulates cell growth and apoptosis, and its constitutive activation has been implicated in the pathogenesis of a variety of malignancies. Recent studies suggest that PI3K/Akt signaling is frequently up-regulated in blast cells from AML patients and strongly contributes to proliferation, survival, and drug-resistance of these cells. Up-regulation of this network in AML may due to several reasons, including FLT3 and Ras activating mutations, increased levels of PI3K p110δ catalytic subunit, lack of PTEN lipid phosphatase expression, and autocrine production of growth factors. Small molecules designed to specifically target key components of this signal transduction network have been shown to induce apoptosis and/or increase conventional drug sensitivity of AML blasts in vitro. Therefore, these inhibitory molecules are being developed for clinical use either as single therapeutic agents or in combination with other forms of therapy. Nevertheless, PI3K/Akt blockade in vivo might have detrimental systemic side effects, given the multiple physiological roles played by this pathway, such as insulin-dependent glucose transport. Herein, we summarize our knowledge about PI3K/Akt signaling in AML and we highlight several pharmacological inhibitors which could be used in the future for treating this too often fatal hematological disorder.
Keywords: Acute myeloid leukaemia, signal transduction, 3-phosphorylated inositol lipids, apoptosis, drug resistance, pharmacological inhibitors
Current Signal Transduction Therapy
Title: The Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway as a Therapeutic Target for the Treatment of Human Acute Myeloid Leukemia (AML)
Volume: 2 Issue: 3
Author(s): Alberto M. Martelli, Giovanna Tabellini, Roberta Bortul, Maria Nyakern, Pier Luigi Tazzari, Camilla Evangelisti and Lucio Cocco
Affiliation:
Keywords: Acute myeloid leukaemia, signal transduction, 3-phosphorylated inositol lipids, apoptosis, drug resistance, pharmacological inhibitors
Abstract: The PI3K/Akt signaling network regulates cell growth and apoptosis, and its constitutive activation has been implicated in the pathogenesis of a variety of malignancies. Recent studies suggest that PI3K/Akt signaling is frequently up-regulated in blast cells from AML patients and strongly contributes to proliferation, survival, and drug-resistance of these cells. Up-regulation of this network in AML may due to several reasons, including FLT3 and Ras activating mutations, increased levels of PI3K p110δ catalytic subunit, lack of PTEN lipid phosphatase expression, and autocrine production of growth factors. Small molecules designed to specifically target key components of this signal transduction network have been shown to induce apoptosis and/or increase conventional drug sensitivity of AML blasts in vitro. Therefore, these inhibitory molecules are being developed for clinical use either as single therapeutic agents or in combination with other forms of therapy. Nevertheless, PI3K/Akt blockade in vivo might have detrimental systemic side effects, given the multiple physiological roles played by this pathway, such as insulin-dependent glucose transport. Herein, we summarize our knowledge about PI3K/Akt signaling in AML and we highlight several pharmacological inhibitors which could be used in the future for treating this too often fatal hematological disorder.
Export Options
About this article
Cite this article as:
Martelli M. Alberto, Tabellini Giovanna, Bortul Roberta, Nyakern Maria, Tazzari Luigi Pier, Evangelisti Camilla and Cocco Lucio, The Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway as a Therapeutic Target for the Treatment of Human Acute Myeloid Leukemia (AML), Current Signal Transduction Therapy 2007; 2 (3) . https://dx.doi.org/10.2174/157436207781745373
DOI https://dx.doi.org/10.2174/157436207781745373 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
- 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
- Announcements
Related Articles
-
Parallel Gene Expression Profiling of Mantle Cell Lymphoma – How Do We Transform ´Omics Data into Clinical Practice
Current Genomics Common and Uncommon Features of Rheumatoid Arthritis and Chronic Obstructive Pulmonary Disease: Clues to a Future Therapy
Current Drug Targets - Immune, Endocrine & Metabolic Disorders DNA Intercalators in Cancer Therapy: Organic and Inorganic Drugs and Their Spectroscopic Tools of Analysis
Mini-Reviews in Medicinal Chemistry Epidemiology of Candida albicans Infections and Role of Non-Candidaalbicans Yeasts
Current Drug Targets Understanding Cancer Drug Resistance by Developing and Studying Resistant Cell Line Models
Current Cancer Drug Targets High-level Soluble Expression, Purification, and Functional Characterization of the Recombinant Human Leukemia Inhibitory Factor: A Potential General Strategy for the Recombinant Expression of Cytokines Consisting of Four α-Helices in a Bundle
Protein & Peptide Letters Serine-Threonine Protein Kinases CK1, CK2 and GSK3 in Normal and Malignant Haematopoiesis
Current Signal Transduction Therapy Medical and Dental Implications of Down Syndrome: A Review Part 1: General and Craniofacial Characteristic
Applied Clinical Research, Clinical Trials and Regulatory Affairs Cytoplasmic CXCR4 High-Expression Exhibits Distinct Poor Clinicopathological Characteristics and Predicts Poor Prognosis in Triple-Negative Breast Cancer
Current Molecular Medicine Exploring Polypharmacology in Drug Discovery and Repurposing Using the CANDO Platform
Current Pharmaceutical Design Targeted Therapy Towards Cancer-A Perspective
Anti-Cancer Agents in Medicinal Chemistry Biosurfactants as a Novel Additive in Pharmaceutical Formulations: Current Trends and Future Implications
Current Drug Metabolism Novel Classes of Dimer Antitumour Drug Candidates
Current Pharmaceutical Design Hemolytic Uremic Syndrome in Children
Current Pediatric Reviews Role of Flavonoids in Future Anticancer Therapy by Eliminating the Cancer Stem Cells
Current Stem Cell Research & Therapy Antibody-Based Preventive and Therapeutic Strategies Against HIV
Current HIV Research Pleiotropic Effect of Mahanine and Girinimbine Analogs: Anticancer Mechanism and its Therapeutic Versatility
Anti-Cancer Agents in Medicinal Chemistry Regulatory Approaches to Nonclinical Reproductive Toxicity Testing of Anti-Cancer Drugs
Anti-Cancer Agents in Medicinal Chemistry Local Drug Delivery Based Treatment Approaches for Effective Management of Periodontitis
Current Drug Therapy Effective Downregulation of BCR-ABL Tumorigenicity by RNA Targeted CRISPR-<i>Cas13a</i>
Current Gene Therapy