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
-
Stimulation of Peroxisome Proliferator-Activated Receptor-Gamma (PPARγ) using Pioglitazone Decreases the Survival of Acute Promyelocytic Leukemia Cells through Up-Regulation of PTEN Expression
Anti-Cancer Agents in Medicinal Chemistry Drug-Drug Interactions of Triazole Antifungal Agents in Multimorbid Patients and Implications for Patient Care
Current Drug Metabolism APO2L/TRAIL: New Insights in the Treatment of Autoimmune Disorders
Recent Patents on Inflammation & Allergy Drug Discovery Hematopoietic Stem Cell Transplantation for Thalassemia
Current Stem Cell Research & Therapy Intracoronary Injection of Drugs to Treat No – Reflow Phenomenon and Microcirculatory Dysfunction
Cardiovascular & Hematological Agents in Medicinal Chemistry Cancer Stem-Cells Patents in the Context of their Therapeutic Purposes: Exploring the Latest Trends (2011-2015)
Recent Patents on Regenerative Medicine Hereditary Papillary Renal Carcinoma Type I
Current Molecular Medicine MicroRNA Involvement in the Pathogenesis of Neuroblastoma: Potential for MicroRNA Mediated Therapeutics
Current Pharmaceutical Design The Cancer Related Thrombotic Tendency in Sepsis
Current Drug Targets The Medical Use of Wheatgrass: Review of the Gap Between Basic and Clinical Applications
Mini-Reviews in Medicinal Chemistry KRAS Mutations in Lung Adenocarcinoma: Molecular and Epidemiological Characteristics, Methods for Detection, and Therapeutic Strategy Perspectives
Current Molecular Medicine The Role of FLT3 Kinase as an AML Therapy Target
Current Pharmaceutical Design Anti-Cancer Therapies that Utilize Cell Penetrating Peptides
Recent Patents on Anti-Cancer Drug Discovery Biological Drugs in Guillain-Barré Syndrome: An Update
Current Neuropharmacology Targeting Apoptosis Pathways in Cancer Therapy
Current Cancer Drug Targets The EGFR Pathway Regulates BCRP Expression in NSCLC Cells: Role of Erlotinib
Current Drug Targets Discovery of Modulators of Protein-Protein Interactions: Current Approaches and Limitations
Current Topics in Medicinal Chemistry Pulmonary Arterial Hypertension in HIV-infected Patients
Current Hypertension Reviews Pterostilbene as a Potential Novel Telomerase Inhibitor: Molecular Docking Studies and Its in vitro Evaluation
Current Pharmaceutical Biotechnology Chemistry and Pharmacology of Angiotensin-Converting Enzyme Inhibitors
Current Pharmaceutical Design