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
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
Deep learning in Single Cell Analysis
The field of biology is undergoing a revolution in our ability to study individual cells at the molecular level, and to integrate data from multiple sources and modalities. This has been made possible by advances in technologies for single-cell sequencing, multi-omics profiling, spatial transcriptomics, and high-throughput imaging, as well as ...read more
New insights on Pediatric Tumors and Associated Cancer Predisposition Syndromes
Because of the broad spectrum of children cancer susceptibility, the diagnosis of cancer risk syndromes in children is rarely used in direct cancer treatment. The field of pediatric cancer genetics and genomics will only continue to expand as a result of increasing use of genetic testing tools. It's possible that ...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
-
HspB1 Dynamic Phospho-Oligomeric Structure Dependent Interactome as Cancer Therapeutic Target
Current Molecular Medicine Patents on Non-Viral Mediated Gene Delivery
Recent Patents on DNA & Gene Sequences Involvement of Leukotriene Pathway in the Pathogenesis of Ischemia- Reperfusion Injury and Septic and Non-Septic Shock
Current Vascular Pharmacology Air Pollution and Lung Cancer
Current Respiratory Medicine Reviews TRPM8, a Sensor for Mild Cooling in Mammalian Sensory Nerve Endings
Current Pharmaceutical Biotechnology MicroRNAs and Cancer; an Overview
Current Pharmaceutical Biotechnology Neuronal Nicotinic Receptors as Brain Targets for Pharmacotherapy of Drug Addiction
CNS & Neurological Disorders - Drug Targets Cancer Gene Therapy with Tissue Inhibitors of Metalloproteinases (TIMPs)
Current Gene Therapy Phenolic Compounds in Prevention and Treatment of Skin Cancers: A Review
Current Medicinal Chemistry The Chemopreventive and Chemotherapeutic Potentials of Tea Polyphenols
Current Pharmaceutical Biotechnology Development of a Berberine Loaded Multifunctional Design for the Treatment of Helicobacter pylori Induced Gastric Ulcer
Drug Delivery Letters The Effects of Cantharidin and Cantharidin Derivates on Tumour Cells
Anti-Cancer Agents in Medicinal Chemistry Pharmacological Roles of the Large-Conductance Calcium-Activated Potassium Channel
Current Topics in Medicinal Chemistry From Natural Products to Small Molecule Ketone Histone Deacetylase Inhibitors: Development of New Class Specific Agents
Current Pharmaceutical Design MIIP, a Cytoskeleton Regulator that Blocks Cell Migration and Invasion, Delays Mitosis, and Suppresses Tumorogenesis
Current Protein & Peptide Science Targeted Therapy of Ovarian Cancer with Angiogenesis Inhibitors
Current Drug Targets Efficacy of Pegylated Lyposomal Anthracyclines and of Intra-Arterial Carboplatin and Doxorubicin Combined with Local Hyperthermia in a Case of Malignant Endovascular Papillary Angioendothelioma
Current Drug Delivery Potential Therapeutic Benefits of Dipyridamole in COVID-19 Patients
Current Pharmaceutical Design Combined Effect of Parthenolide and Various Anti-cancer Drugs or Anticancer Candidate Substances on Malignant Cells in vitro and in vivo
Mini-Reviews in Medicinal Chemistry Competition Between Tumor and Mononuclear Phagocyte System Causing the Low Tumor Distribution of Nanoparticles and Strategies to Improve Tumor Accumulation
Current Drug Delivery