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 |
- 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
-
Targeting ATP7A to Increase the Sensitivity of Neuroblastoma Cells to Retinoid Therapy
Current Cancer Drug Targets Human Mesenchymal Stem Cells (hMSCs) as Targets of DNA Damaging Agents in Cancer Therapy
Current Cancer Drug Targets Genetics of Bladder Malignant Tumors in Childhood
Current Genomics GVHD: Complication and Challenge to Successful Allogeneic Hematopoietic Cell Transplantation
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents HtrA Serine Proteases as Potential Therapeutic Targets in Cancer
Current Cancer Drug Targets Current Therapeutic Alternatives and New Perspectives in Glioblastoma Multiforme
Current Medicinal Chemistry Cancer Stem Cells: A New Paradigm for Understanding Tumor Growth and Progression and Drug Resistance
Current Medicinal Chemistry Genetic Polymorphisms of Drug Metabolizing Enzymes and Transporters: The Long Way from Bench to Bedside
Current Topics in Medicinal Chemistry Targeting Apoptosis Resistance in Rhabdomyosarcoma
Current Cancer Drug Targets Advances in Interleukin-12 Gene Therapy for Acquired Liver Diseases
Current Gene Therapy Role of Tyrosine Phosphatase Inhibitors in Cancer Treatment with Emphasis on SH2 Domain-Containing Tyrosine Phosphatases (SHPs)
Anti-Cancer Agents in Medicinal Chemistry Molecular Pathogenesis of Philadelphia Chromosome Negative Chronic Myeloproliferative Neoplasms
Current Cancer Drug Targets Human Immunodeficiency Virus-Associated Malignancies: A Therapeutic Update
Current HIV Research Diagnosis and Treatment of Pulmonary Fungal Infections in Critically Ill Patients
Current Respiratory Medicine Reviews Biological Therapy of Hematologic Malignancies: Toward a Chemotherapy- free Era
Current Medicinal Chemistry Ex Vivo Liver – Directed Gene Therapy for the Treatment of Metabolic Diseases: Advances in Hepatocyte Transplantation and Retroviral Vectors
Current Gene Therapy HtrA Protease Family as Therapeutic Targets
Current Pharmaceutical Design 5-Benzylidene-3,4-dihalo-furan-2-one derivatives inhibit human leukemia cancer cells through suppression of NF-κB and GSK-3β
Anti-Cancer Agents in Medicinal Chemistry Preclinical Studies of PROTACs in Hematological Malignancies
Cardiovascular & Hematological Disorders-Drug Targets Monoclonal Antibodies in the Management of Solid Tumors
Current Topics in Medicinal Chemistry