Abstract
PKB/AKT constitutes an important pathway that regulates the signaling of multiple essential biological processes. PTEN is a dual protein/lipid phosphatase whose main substrate is phosphatidyl-inositol,3,4,5 triphosphate (PIP3), the product of PI3K. Increases in PIP3 result in the recruitment of PDK1 and AKT to the membrane where they are activated. Furthermore, PI3K can be activated by direct binding to oncogenic Ras proteins. Many components of this pathway have been described as genetically altered in cancer. PTEN activity is lost by mutations, deletions or promoter methylation at high frequency in many primary and metastatic human cancers, and some germline mutations of PTEN are found in several familial cancer predisposition syndromes. Activating mutations of PI3K occur in human tumors and confer tumorigenic properties to cells in culture. Taken together, this evidence indicates that the AKT pathway is a promising potential target for cancer chemotherapy. Indeed, many companies and academic laboratories have initiated a variety of approaches to inhibit the pathway at different points. Essentially, PI3Ks, PDK1, AKT and mTOR are heavily targeted for therapy in different ways. These proteins are kinases, which are very “druggable” targets a priori, and, according to the “addiction hypothesis”, cancer cells with the activated pathway will be more dependent on its activity for their survival.
Keywords: PKB/AKT, cancer, tumorigenesis, PI3K, PTEN
Current Pharmaceutical Design
Title: The PKB/AKT Pathway in Cancer
Volume: 16 Issue: 1
Author(s): Amancio Carnero
Affiliation:
Keywords: PKB/AKT, cancer, tumorigenesis, PI3K, PTEN
Abstract: PKB/AKT constitutes an important pathway that regulates the signaling of multiple essential biological processes. PTEN is a dual protein/lipid phosphatase whose main substrate is phosphatidyl-inositol,3,4,5 triphosphate (PIP3), the product of PI3K. Increases in PIP3 result in the recruitment of PDK1 and AKT to the membrane where they are activated. Furthermore, PI3K can be activated by direct binding to oncogenic Ras proteins. Many components of this pathway have been described as genetically altered in cancer. PTEN activity is lost by mutations, deletions or promoter methylation at high frequency in many primary and metastatic human cancers, and some germline mutations of PTEN are found in several familial cancer predisposition syndromes. Activating mutations of PI3K occur in human tumors and confer tumorigenic properties to cells in culture. Taken together, this evidence indicates that the AKT pathway is a promising potential target for cancer chemotherapy. Indeed, many companies and academic laboratories have initiated a variety of approaches to inhibit the pathway at different points. Essentially, PI3Ks, PDK1, AKT and mTOR are heavily targeted for therapy in different ways. These proteins are kinases, which are very “druggable” targets a priori, and, according to the “addiction hypothesis”, cancer cells with the activated pathway will be more dependent on its activity for their survival.
Export Options
About this article
Cite this article as:
Carnero Amancio, The PKB/AKT Pathway in Cancer, Current Pharmaceutical Design 2010; 16 (1) . https://dx.doi.org/10.2174/138161210789941865
DOI https://dx.doi.org/10.2174/138161210789941865 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
![](/images/wayfinder.jpg)
- 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
- Announcements
Related Articles
-
Iodinated Contrast Media in Diagnostic Imaging: Cardiovascular Side Effects
Current Pharmacogenomics and Personalized Medicine Pharmacologic Therapy in Growth Hormone Disorders and the Heart
Current Medicinal Chemistry Incidence and Prevalence of Hypothyroidism in Patients Affected by Chronic Heart Failure: Role of Amiodarone
Endocrine, Metabolic & Immune Disorders - Drug Targets Genomic Databases and the Search of Protein Targets for Protozoan Parasites
Current Drug Targets Strategy for a Genetic Assessment of Antipsychotic and Antidepressant- Related Proarrhythmia
Current Medicinal Chemistry Hypoxia and Fetal Heart Development
Current Molecular Medicine Efficacy of Enzyme Replacement Therapy in Fabry Disease
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Comparison of High-Sensitive CRP, RDW, PLR and NLR between Patients with Chronic Obstructive Pulmonary Disease and Chronic Heart Failure
Current Respiratory Medicine Reviews Scaffold Hopping for Identification of Novel PKCβII Inhibitors Based on Ligand and Structural Approaches, Virtual Screening and Molecular Dynamics Study
Combinatorial Chemistry & High Throughput Screening Antioxidant Properties of Melatonin and its Potential Action in Diseases
Current Topics in Medicinal Chemistry A Decrease in the Cellular Phosphodiester to Phosphomonoester Lipid Ratio is Characteristic of HIV-1 Infection
Current HIV Research Patent Selections
Recent Patents on Cardiovascular Drug Discovery Demystifying the ACE Polymorphism: From Genetics to Biology
Current Pharmaceutical Design Hypertension in Type 2 Diabetes Mellitus: Do We Need to Redefine the Role of Sulfonylureas?
Recent Advances in Cardiovascular Drug Discovery (Discontinued) Current and Future Prospective of a Versatile Moiety: Imidazole
Current Drug Targets Chagas Disease: Progress and New Perspectives
Current Medicinal Chemistry Animal Modeling of Cancer Pathology and Studying Tumor Response to Therapy
Current Drug Targets “Seeing is Believing”: Perspectives of Applying Imaging Technology in Discovery Toxicology
Combinatorial Chemistry & High Throughput Screening Gene Patents in the Primary Prevention of Vascular Diseases
Recent Patents on DNA & Gene Sequences A Review of Systemic Vasodilators in Low Cardiac Output Syndrome Following Pediatric Cardiac Surgery
Current Vascular Pharmacology