Abstract
The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in human cancer and represents an attractive target for therapies based on small molecule inhibitors. PI3K isoforms play an essential role in the signal transduction events activated by cell surface receptors including receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs). There are eight known PI3K isoforms in humans, which have been subdivided into three classes (I-III). Therefore PI3Ks show considerable diversity and it remains unclear which kinases in this family should be targeted in cancer. The class IA of PI3K comprises the p110α, p110β and p110δ isoforms, which associate with activated RTKs. In human cancer, recent reports have described activating mutations in the PIK3CA gene encoding p110α, and inactivating mutations in the phosphatase and tensin homologue (PTEN) gene, a tumour suppressor and antagonist of the PI3K pathway. The PIK3CA mutations described in cancer constitutively activate p110α and, when expressed in cells drive oncogenic transformation. Moreover, these mutations cause the constitutive activation of downstream signaling molecules such as Akt/protein kinase B (PKB), mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6K) that is commonly observed in cancer cells. In addition to p110α, the other isoforms of the PI3K family may also play a role in human cancer, although their individual functions remain to be precisely identified. In this review we will discuss the evidence implicating individual PI3K isoforms in human cancer and their potential as drug targets in this context.
Keywords: Akt signaling, angiogenesis, phosphorylation, FOXO proteins, metastasis
Current Genomics
Title: The Phosphoinositide 3-Kinase Pathway in Human Cancer: Genetic Alterations and Therapeutic Implications
Volume: 8 Issue: 5
Author(s): Alexandre Arcaro and Ana S. Guerreiro
Affiliation:
Keywords: Akt signaling, angiogenesis, phosphorylation, FOXO proteins, metastasis
Abstract: The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in human cancer and represents an attractive target for therapies based on small molecule inhibitors. PI3K isoforms play an essential role in the signal transduction events activated by cell surface receptors including receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs). There are eight known PI3K isoforms in humans, which have been subdivided into three classes (I-III). Therefore PI3Ks show considerable diversity and it remains unclear which kinases in this family should be targeted in cancer. The class IA of PI3K comprises the p110α, p110β and p110δ isoforms, which associate with activated RTKs. In human cancer, recent reports have described activating mutations in the PIK3CA gene encoding p110α, and inactivating mutations in the phosphatase and tensin homologue (PTEN) gene, a tumour suppressor and antagonist of the PI3K pathway. The PIK3CA mutations described in cancer constitutively activate p110α and, when expressed in cells drive oncogenic transformation. Moreover, these mutations cause the constitutive activation of downstream signaling molecules such as Akt/protein kinase B (PKB), mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6K) that is commonly observed in cancer cells. In addition to p110α, the other isoforms of the PI3K family may also play a role in human cancer, although their individual functions remain to be precisely identified. In this review we will discuss the evidence implicating individual PI3K isoforms in human cancer and their potential as drug targets in this context.
Export Options
About this article
Cite this article as:
Arcaro Alexandre and Guerreiro S. Ana, The Phosphoinositide 3-Kinase Pathway in Human Cancer: Genetic Alterations and Therapeutic Implications, Current Genomics 2007; 8 (5) . https://dx.doi.org/10.2174/138920207782446160
DOI https://dx.doi.org/10.2174/138920207782446160 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Related Journals
- 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
-
Gene Therapy of Cancer with Interleukin-12
Current Pharmaceutical Design Antimicrobial Peptides in Oral Cancer
Current Pharmaceutical Design Power from the Garden: Plant Compounds as Inhibitors of the Hallmarks of Cancer
Current Medicinal Chemistry QbD Approach For Anti-Cancer Drugs - A Review
Current Pharmaceutical Analysis Midkine: A Promising Molecule for Drug Development to Treat Diseases of the Central Nervous System
Current Pharmaceutical Design Recent Updates on the Therapeutic Potential of HER2 Tyrosine Kinase Inhibitors for the Treatment of Breast Cancer
Current Cancer Drug Targets Bugs and Drugs: Oncolytic Virotherapy in Combination with Chemotherapy
Current Pharmaceutical Biotechnology Current Trends in Cancer Biomarker Discovery Using Urinary Metabolomics: Achievements and New Challenges
Current Medicinal Chemistry Progress in the Development of Aminopeptidase N (APN/CD13) Inhibitors
Current Medicinal Chemistry - Anti-Cancer Agents Association of Viruses in the Development of Cardiovascular Diseases
Current Pharmaceutical Design Role of Carbon Monoxide in Kidney Function: Is a little Carbon Monoxide Good for the Kidney?
Current Pharmaceutical Biotechnology Advanced Techniques for Penetration Enhancement in Transdermal Drug Delivery System
Current Drug Delivery Inflammatory and Non-Inflammatory Roles for Toll-Like Receptors in Gastrointestinal Cancer
Current Pharmaceutical Design Cancer Stem Cell Markers in Nasopharyngeal Carcinoma and Its Relevance for Therapy
Current Traditional Medicine Light Directed Gene Transfer by Photochemical Internalisation
Current Gene Therapy Partners in Crime: NGF and BDNF in Visceral Dysfunction
Current Neuropharmacology Multiple Roles of Transient Receptor Potential (TRP) Channels in Inflammatory Conditions and Current Status of Drug Development
Current Topics in Medicinal Chemistry Comparative Safety Assessment Study for Drospirenone Induced Gallbladder Diseases Using the Adverse Drug Reaction Database of USA, Europe, and Canada
Current Drug Safety Near-infrared Light Responsive Upconversion Nanoparticles for Imaging, Drug Delivery and Therapy of Cancers
Current Nanoscience The Linkage Between Inflammation and Immune Tolerance: Interfering with Inflammation in Cancer
Current Cancer Drug Targets