Abstract
Phosphatidylinositol 3-kinase (PI3K), a heterodimeric lipid kinase, is a key enzyme in signal transduction from various stimuli to downstream pathways that elicit diverse responses involving growth, proliferation, survival, differentiation, and metabolism in many cellular systems. Activated PI3K generates phosphatidylinositol-3,4,5-triphosphate, which recruits phosphatidylinositol-dependent kinase 1 (PDK1) and Akt serine/threonine kinase at the plasma membrane, resulting in activation of Akt. In turn, Akt activates multiple downstream targets, most notably the mTOR pathway. There is abundant evidence implicating the PI3K/Akt/mTOR pathway in the development and progression of a variety of tumors including hematologic neoplasms. Therefore, this pathway is considered a critical target for cancer therapy. We review the regulatory mechanisms of the PI3K/Akt/mTOR signaling pathway and the role of this pathway in oncogenesis of hematological malignancies.
Keywords: PI3K, Akt, mTOR, hematologic malignancies
Anti-Cancer Agents in Medicinal Chemistry
Title: Regulation and Importance of the PI3K/Akt/mTOR Signaling Pathway in Hematologic Malignancies
Volume: 9 Issue: 9
Author(s): Kiyotaka Kawauchi, Toshie Ogasawara, Masako Yasuyama, Kuniaki Otsuka and Osamu Yamada
Affiliation:
Keywords: PI3K, Akt, mTOR, hematologic malignancies
Abstract: Phosphatidylinositol 3-kinase (PI3K), a heterodimeric lipid kinase, is a key enzyme in signal transduction from various stimuli to downstream pathways that elicit diverse responses involving growth, proliferation, survival, differentiation, and metabolism in many cellular systems. Activated PI3K generates phosphatidylinositol-3,4,5-triphosphate, which recruits phosphatidylinositol-dependent kinase 1 (PDK1) and Akt serine/threonine kinase at the plasma membrane, resulting in activation of Akt. In turn, Akt activates multiple downstream targets, most notably the mTOR pathway. There is abundant evidence implicating the PI3K/Akt/mTOR pathway in the development and progression of a variety of tumors including hematologic neoplasms. Therefore, this pathway is considered a critical target for cancer therapy. We review the regulatory mechanisms of the PI3K/Akt/mTOR signaling pathway and the role of this pathway in oncogenesis of hematological malignancies.
Export Options
About this article
Cite this article as:
Kawauchi Kiyotaka, Ogasawara Toshie, Yasuyama Masako, Otsuka Kuniaki and Yamada Osamu, Regulation and Importance of the PI3K/Akt/mTOR Signaling Pathway in Hematologic Malignancies, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (9) . https://dx.doi.org/10.2174/187152009789377772
DOI https://dx.doi.org/10.2174/187152009789377772 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- 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
-
The Therapeutic Target Hsp90 and Cancer Hallmarks
Current Pharmaceutical Design “Virostatics” as a Potential New Class of HIV Drugs
Current Pharmaceutical Design Molecular Targeting of Protein Kinases to Optimize Selectivity and Resistance Profiles of Kinase Inhibitors
Current Topics in Medicinal Chemistry Insight to Pharmacokinetics of TKIs: Optimizing Practical Guidelines for Individualized Therapy
Current Drug Metabolism The Akt Pathway: Molecular Targets for Anti-Cancer Drug Development
Current Cancer Drug Targets New Candidate Genes for Lack of Sensitivity to Therapy in Pediatric Leukemias
Current Cancer Drug Targets Non Steroidal Anti Inflammatory Drugs As Gatekeepers Of Colon Carcinoma Highlight New Scenarios Beyond Cyclooxygenases Inhibition
Current Cancer Drug Targets Novel Rational Drug Design Strategies with Potential to Revolutionize Malaria Chemotherapy
Current Medicinal Chemistry Epigenetic Targets and their Inhibitors in Cancer Therapy
Current Topics in Medicinal Chemistry MiRNA-103b Downregulates ITGB3 and Mediates Apoptosis in Ex Vivo Stored Human Platelets
MicroRNA Anti-Interleukin-6 Receptor Antibody Therapy in Rheumatic Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Retracted: miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway
Anti-Cancer Agents in Medicinal Chemistry Signaling Pathways Modulating Dependence of Lung Cancer on Mutant Epidermal Growth Factor Receptor and Mechanisms of Intrinsic and Acquired Resistance to Tyrosine Kinase Inhibitors
Current Pharmaceutical Design Inhibitors of Apoptosis Proteins (IAPs) as Potential Molecular Targets for Therapy of Hematological Malignancies
Current Molecular Medicine Insulin-Like Growth Factor 1 Receptor Targeted Therapeutics: Novel Compounds and Novel Treatment Strategies for Cancer Medicine
Recent Patents on Anti-Cancer Drug Discovery Multifaceted Mechanisms for Cell Survival and Drug Targeting in Chronic Myelogenous Leukemia
Current Cancer Drug Targets Interleukin 2 in Cancer Therapy
Current Medicinal Chemistry Small Molecule Toxins Targeting Tumor Receptors
Current Pharmaceutical Design Isocitrate Dehydrogenase 2 Inhibitors for the Treatment of Hematologic Malignancies: Advances and Future Opportunities
Mini-Reviews in Medicinal Chemistry Peroxisome Proliferator-Activated Receptors: Role of Isoform Gamma in the Antineoplastic Effect of Iodine in Mammary Cancer
Current Cancer Drug Targets