Abstract
Phosphatidylinositol 3-kinases (PI3Ks) are key molecules in the signal transduction pathways initiated by the binding of extracellular signals to their cell surface receptors. The PI3K family of enzymes comprises eight catalytic isoforms subdivided into three classes and control a variety of cellular processes including proliferation, growth, apoptosis, migration and metabolism. Deregulation of the PI3K pathway has been extensively investigated in connection to cancer, but is also involved in other commonly occurring diseases such as chronic inflammation, autoimmunity, allergy, atherosclerosis, cardiovascular and metabolic diseases. The fact that the PI3K pathway is deregulated in a large number of human diseases, and its importance for different cellular responses, makes it an attractive drug target. Pharmacological PI3K inhibitors have played a very important role in studying cellular responses involving these enzymes. Currently, a wide range of selective PI3K inhibitors have been tested in preclinical studies and some have entered clinical trials in oncology. However, due to the complexity of PI3K signaling pathways, developing an effective anti-cancer therapy may be difficult. The biggest challenge in curing cancer patients with various signaling pathway abnormalities is to target multiple components of different signal transduction pathways with mechanism-based combinatorial treatments. In this article we will give an overview of the complex role of PI3K isoforms in human diseases and discuss their potential as drug targets. In addition, we will describe the drugs currently used in clinical trials, as well as promising emerging candidates.
Keywords: Phosphatidylinositol 3-kinases (PI3Ks), cancer, autoimmune and cardiovascular diseases, ATP-competitive small molecule inhibitors, PI3K/Akt signaling pathway, isoform, mouse model, inflammatory, mutation
Current Drug Targets
Title: Phosphatidylinositol 3-Kinase Isoforms as Novel Drug Targets
Volume: 12 Issue: 7
Author(s): Karolina Blajecka, Anna Borgstrom and Alexandre Arcaro
Affiliation:
Keywords: Phosphatidylinositol 3-kinases (PI3Ks), cancer, autoimmune and cardiovascular diseases, ATP-competitive small molecule inhibitors, PI3K/Akt signaling pathway, isoform, mouse model, inflammatory, mutation
Abstract: Phosphatidylinositol 3-kinases (PI3Ks) are key molecules in the signal transduction pathways initiated by the binding of extracellular signals to their cell surface receptors. The PI3K family of enzymes comprises eight catalytic isoforms subdivided into three classes and control a variety of cellular processes including proliferation, growth, apoptosis, migration and metabolism. Deregulation of the PI3K pathway has been extensively investigated in connection to cancer, but is also involved in other commonly occurring diseases such as chronic inflammation, autoimmunity, allergy, atherosclerosis, cardiovascular and metabolic diseases. The fact that the PI3K pathway is deregulated in a large number of human diseases, and its importance for different cellular responses, makes it an attractive drug target. Pharmacological PI3K inhibitors have played a very important role in studying cellular responses involving these enzymes. Currently, a wide range of selective PI3K inhibitors have been tested in preclinical studies and some have entered clinical trials in oncology. However, due to the complexity of PI3K signaling pathways, developing an effective anti-cancer therapy may be difficult. The biggest challenge in curing cancer patients with various signaling pathway abnormalities is to target multiple components of different signal transduction pathways with mechanism-based combinatorial treatments. In this article we will give an overview of the complex role of PI3K isoforms in human diseases and discuss their potential as drug targets. In addition, we will describe the drugs currently used in clinical trials, as well as promising emerging candidates.
Export Options
About this article
Cite this article as:
Blajecka Karolina, Borgstrom Anna and Arcaro Alexandre, Phosphatidylinositol 3-Kinase Isoforms as Novel Drug Targets, Current Drug Targets 2011; 12 (7) . https://dx.doi.org/10.2174/138945011795677773
DOI https://dx.doi.org/10.2174/138945011795677773 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response, and/or therapy ...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
-
Older and Newer Strategies for the Pharmacological Management of Agitation in Patients with Bipolar Disorder or Schizophrenia
CNS & Neurological Disorders - Drug Targets Modulation of Gi Proteins in Hypertension: Role of Angiotensin II and Oxidative Stress
Current Cardiology Reviews Current Concepts of Immunopathogenesis, Diagnosis and Therapy in Whipples Disease
Current Medicinal Chemistry Physiology, Pharmacology and Pathophysiology of the pH Regulatory Transport Proteins NHE1 and NBCn1: Similarities, Differences, and Implications for Cancer Therapy
Current Pharmaceutical Design BACE1 Dependent Neuregulin Processing: Review
Current Alzheimer Research Extrahepatic Metabolism may Complicate the IVIVC in Rats
Drug Metabolism Letters Cardiac Adrenomedullin: Its Role in Cardiac Hypertrophy and Heart Failure
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Synthetic Curcumin Analog UBS109 Inhibits the Growth of Head and Neck Squamous Cell Carcinoma Xenografts
Current Cancer Drug Targets Chlorogenic Acid Suppresses a Cell Adhesion Molecule in Experimental Autoimmune Myocarditis in Mice
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Fenofibrate: Metabolic and Pleiotropic Effects
Current Vascular Pharmacology Pharmacological Properties of Physical Exercise in The Elderly
Current Pharmaceutical Design Towards a Unified Theory of Calmodulin Regulation (Calmodulation) of Voltage-Gated Calcium and Sodium Channels
Current Molecular Pharmacology Markers of Atherosclerotic Disease: What do they Mean? Current Opinion and Future Trends
Current Pharmaceutical Design The Promise of Plant-Derived Substances as Inhibitors of Arginase
Mini-Reviews in Medicinal Chemistry Rationale and Design of an Observational Study to Determine the Effects of Cholecalciferol on Hypertension, Proteinuria and Urinary MCP-1 in ADPKD
Current Hypertension Reviews Endogenous Retroelements in Cellular Senescence and Related Pathogenic Processes: Promising Drug Targets in Age-Related Diseases
Current Drug Targets Drug-Induced Liver Injury: Mechanisms, Types and Biomarkers
Current Medicinal Chemistry Alcoholic/Nonalcoholic Fatty Liver Disease Detection with Transient Elastography: A Detailed Review and Meta-analysis
Current Medical Imaging Empagliflozin and the Diabetic Kidney: Pathophysiological Concepts and Future Challenges
Endocrine, Metabolic & Immune Disorders - Drug Targets Melatonin Regulates Angiogenic and Inflammatory Proteins in MDA-MB-231 Cell Line and in Co-culture with Cancer-associated Fibroblasts
Anti-Cancer Agents in Medicinal Chemistry