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
-
Targeting the Akt Kinase to Modulate Survival, Invasiveness and Drug Resistance of Cancer Cells
Current Medicinal Chemistry Clinical Trial Update and Novel Therapeutic Approaches for Metastatic Prostate Cancer
Current Medicinal Chemistry Ruthenium Complexes as Anticancer Agents
Current Medicinal Chemistry Subject Index To Volume 2
Current Drug Targets The Role of ING Tumor Suppressors in UV Stress Response and Melanoma Progression
Current Drug Targets Imaging of Spinal Bone Tumors: Principles and Practice
Current Medical Imaging Anti Tumor Necrosis Factor-a Monoclonal Antibody (Infliximab) Therapy in Patients with Inflammatory Bowel Disease (IBD): Applications and Side Effects
Drug Design Reviews - Online (Discontinued) Epigenetic Mechanisms of Therapy Resistance in Diffuse Large B Cell Lymphoma (DLBCL)
Current Cancer Drug Targets Emerging Indications for Statins: A Pluripotent Family of Agents with Several Potential Applications
Current Pharmaceutical Design Implication of Raft Microdomains in Drug Induced Apoptosis
Current Medicinal Chemistry - Anti-Cancer Agents Antineoplastic Chemotherapy Induced QTc Prolongation
Current Drug Safety Antiangiogenic Therapy
Current Pharmaceutical Design Drug-Glycosidation and Drug Development
Mini-Reviews in Medicinal Chemistry Caffeic Acid Phenethyl Ester Effects: In Silico Study of its Osteoimmunological Mechanisms
Letters in Drug Design & Discovery Lipoamino Acid Prodrugs of Paclitaxel: Synthesis and Cytotoxicity Evaluation on Human Anaplastic Thyroid Carcinoma Cells
Current Cancer Drug Targets Cancer Prevention and Therapy in a Preclinical Mouse Model: Impact of FHIT Viruses
Current Gene Therapy Ceramide in Chemotherapy of Tumors
Recent Patents on Anti-Cancer Drug Discovery Pleiotropic Functions of Rho GTPase Signaling: A Trojan Horse or Achilles Heel for Breast Cancer Treatment?
Current Drug Targets Interaction of Human Herpesvirus 8 Viral Interleukin-6 with Human Interleukin-6 Receptor Using <i>In Silico</i> Approach: The Potential Role in HHV-8 Pathogenesis
Current Proteomics Engineering Approaches to Develop the Next Generation of Antibodies to Respiratory Targets
Inflammation & Allergy - Drug Targets (Discontinued)