Abstract
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a central role in growth, proliferation, and anti-apoptotic mechanisms to promote cell cycle and survival not only in normal cells but also in a variety of tumor cells. Thus, the PI3K/Akt pathway, including the downstream effectors, may be a critical target for cancer therapy. Although this pathway has been investigated rigorously and dissected in detail in many physiological systems, its role in molecular target therapy for cancer remains to be established. Hematological malignancies such as leukemia, lymphoma, and myeloma can be ideal models for molecular targeting therapy because of the ease in obtaining samples for examining the effect of inhibitors of target molecules with critical roles in tumor growth and progression. In fact, several inhibitors, such as imatinib in Philadelphia chromosome-positive leukemia and bortezomib in multiple myeloma, have proved quite useful in clinics. Because the PI3K/Akt pathway is active in various hematological malignancies, inhibitors related to this pathway have been confirmed to induce apoptosis in these tumor cells. Efforts to exploit selective inhibitors of the PI3K/Akt pathway that show effectiveness and safety in the clinical setting are underway. We review the recent progress in molecular targeting therapy for the PI3K/Akt pathway in hematologic malignancies.
Keywords: PI3K, Akt, molecular targeting therapy, hematologic malignancies
Anti-Cancer Agents in Medicinal Chemistry
Title: The PI3K/Akt Pathway as a Target in the Treatment of Hematologic Malignancies
Volume: 9 Issue: 5
Author(s): Kiyotaka Kawauchi, Toshie Ogasawara, Masako Yasuyama, Kuniaki Otsuka and Osamu Yamada
Affiliation:
Keywords: PI3K, Akt, molecular targeting therapy, hematologic malignancies
Abstract: The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a central role in growth, proliferation, and anti-apoptotic mechanisms to promote cell cycle and survival not only in normal cells but also in a variety of tumor cells. Thus, the PI3K/Akt pathway, including the downstream effectors, may be a critical target for cancer therapy. Although this pathway has been investigated rigorously and dissected in detail in many physiological systems, its role in molecular target therapy for cancer remains to be established. Hematological malignancies such as leukemia, lymphoma, and myeloma can be ideal models for molecular targeting therapy because of the ease in obtaining samples for examining the effect of inhibitors of target molecules with critical roles in tumor growth and progression. In fact, several inhibitors, such as imatinib in Philadelphia chromosome-positive leukemia and bortezomib in multiple myeloma, have proved quite useful in clinics. Because the PI3K/Akt pathway is active in various hematological malignancies, inhibitors related to this pathway have been confirmed to induce apoptosis in these tumor cells. Efforts to exploit selective inhibitors of the PI3K/Akt pathway that show effectiveness and safety in the clinical setting are underway. We review the recent progress in molecular targeting therapy for the PI3K/Akt pathway in hematologic malignancies.
Export Options
About this article
Cite this article as:
Kawauchi Kiyotaka, Ogasawara Toshie, Yasuyama Masako, Otsuka Kuniaki and Yamada Osamu, The PI3K/Akt Pathway as a Target in the Treatment of Hematologic Malignancies, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (5) . https://dx.doi.org/10.2174/187152009788451851
DOI https://dx.doi.org/10.2174/187152009788451851 |
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
-
Molecular Dynamics and Structural Studies of the Ets Domain-DNA Complexes
Current Bioinformatics The Role of C-Reactive Protein in Atherosclerotic Cardiovascular Disease: An Overview
Current Vascular Pharmacology Anticancer Antifolates: Current Status and Future Directions
Current Pharmaceutical Design Oxidative Stress, Redox Signaling and Cancer Chemoresistance: Putting Together the Pieces of the Puzzle
Current Medicinal Chemistry Targeted α-Particle Therapy: A Clinical Overview
Current Radiopharmaceuticals Monitoring Therapy with Gene Expression Profiling Reveals Physiological Differences in Drug Action
Current Pharmaceutical Design Promotion of Metastasis-associated Gene Expression in Survived PANC-1 Cells Following Trichostatin A Treatment
Anti-Cancer Agents in Medicinal Chemistry Current Advances in Delivery of Biotherapeutics Across the Blood-Brain Barrier
Current Drug Discovery Technologies Adipokines, Metabolism and the Immune Response in the Regulation of Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Bcl-2 Targeted-Therapy for the Treatment of Head and Neck Squamous Cell Carcinoma
Recent Patents on Anti-Cancer Drug Discovery EGF-R Small Inhibitors and Anti-EGF-R Antibodies: Advantages and Limits of a New Avenue in Anticancer Therapy
Recent Patents on Anti-Cancer Drug Discovery New Strategies and Biological Agents in the Treatment of Autoimmune Inflammatory Diseases. Progress and Challenges
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Radiolabeled Nucleosides for Predicting and Monitoring the Cancer Therapeutic Efficacy of Chemodrugs
Current Medicinal Chemistry Fibrillar, Fibril-associated and Basement Membrane Collagens of the Arterial Wall: Architecture, Elasticity and Remodeling Under Stress
Current Pharmaceutical Design Modulation of Tumour-Related Signaling Pathways by Natural Pentacyclic Triterpenoids and their Semisynthetic Derivatives
Current Medicinal Chemistry MRI of the Small and Large Bowel
Current Medical Imaging Anticarcinogenic Actions of Tributyrin, A Butyric Acid Prodrug
Current Drug Targets Quantum Dots in the Therapy: Current Trends and Perspectives
Mini-Reviews in Medicinal Chemistry The miRNAs and Epithelial-Mesenchymal Transition in Cancers
Current Pharmaceutical Design Lectins in Human Cancer: Both a Devil and an Angel?
Current Protein & Peptide Science