Abstract
Protein phosphorylation catalyzed by protein kinases plays critical roles in the regulation of signal-transduction pathways. Deregulated kinase activity is observed in a variety of human diseases, such as cancer, making them targets for the development of molecular therapies. The PI3K/PTEN/AKT/mTOR and RAF/MEK/ERK signaling pathways play fundamental roles in transmitting signals from membrane receptors to downstream targets that regulate apoptosis, cell growth and angiogenesis. Accumulating evidence suggests that both pathways are constitutively activated through multiple genetic and epigenetic mechanisms in a wide variety of human malignancies and play several key functions in cancer development and progression; in that respect, both the PI3K and MAPK pathways function at the bottleneck of signal transduction through protein kinase cascades, thereby constituting attractive therapeutic targets for anti-cancer treatments. These pathways, however, are part of complicated and interwoven regulatory networks and recent evidence suggests that combining inhibitors targeting both the PI3K/PTEN/AKT/mTOR and the RAF/MEK/ERK pathways may avoid tumor escape from single-pathway blockade and ultimately suppress both malignant growth and survival more efficiently. Moreover, both pathways may converge on the regulation of crucial functions, such as neo-angiogenesis, involving not only the cancer cell but also the tumor stroma and the surrounding “normal” compartment. In this review, we describe recent advances in understanding the PI3K and MAPK pathways, in particular the mechanisms by which they regulate tumor growth and angiogenesis, and highlight the potential therapeutic opportunities for targeting these pathways for cancer treatment.
Current Signal Transduction Therapy
Title: Signaling Intermediates (PI3K/PTEN/AKT/mTOR and RAF/MEK/ERK Pathways) as Therapeutic Targets for Anti-Cancer and Anti-Angiogenesis Treatments
Volume: 4 Issue: 2
Author(s): Ludovica Ciuffreda, James A. McCubrey and Michele Milella
Affiliation:
Abstract: Protein phosphorylation catalyzed by protein kinases plays critical roles in the regulation of signal-transduction pathways. Deregulated kinase activity is observed in a variety of human diseases, such as cancer, making them targets for the development of molecular therapies. The PI3K/PTEN/AKT/mTOR and RAF/MEK/ERK signaling pathways play fundamental roles in transmitting signals from membrane receptors to downstream targets that regulate apoptosis, cell growth and angiogenesis. Accumulating evidence suggests that both pathways are constitutively activated through multiple genetic and epigenetic mechanisms in a wide variety of human malignancies and play several key functions in cancer development and progression; in that respect, both the PI3K and MAPK pathways function at the bottleneck of signal transduction through protein kinase cascades, thereby constituting attractive therapeutic targets for anti-cancer treatments. These pathways, however, are part of complicated and interwoven regulatory networks and recent evidence suggests that combining inhibitors targeting both the PI3K/PTEN/AKT/mTOR and the RAF/MEK/ERK pathways may avoid tumor escape from single-pathway blockade and ultimately suppress both malignant growth and survival more efficiently. Moreover, both pathways may converge on the regulation of crucial functions, such as neo-angiogenesis, involving not only the cancer cell but also the tumor stroma and the surrounding “normal” compartment. In this review, we describe recent advances in understanding the PI3K and MAPK pathways, in particular the mechanisms by which they regulate tumor growth and angiogenesis, and highlight the potential therapeutic opportunities for targeting these pathways for cancer treatment.
Export Options
About this article
Cite this article as:
Ciuffreda Ludovica, McCubrey A. James and Milella Michele, Signaling Intermediates (PI3K/PTEN/AKT/mTOR and RAF/MEK/ERK Pathways) as Therapeutic Targets for Anti-Cancer and Anti-Angiogenesis Treatments, Current Signal Transduction Therapy 2009; 4 (2) . https://dx.doi.org/10.2174/157436209788167466
DOI https://dx.doi.org/10.2174/157436209788167466 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Nitrone Derivatives as Therapeutics: From Chemical Modification to Specific-targeting
Current Topics in Medicinal Chemistry Synthesis of Silica Based Nanoparticles Against the Proliferation of Human Prostate Cancer
Anti-Cancer Agents in Medicinal Chemistry Potentials of Polymeric Nanoparticle as Drug Carrier for Cancer Therapy: With a Special Reference to Pharmacokinetic Parameters
Current Drug Metabolism The Synthesis of Nano-Doxorubicin and its Anticancer Effect
Anti-Cancer Agents in Medicinal Chemistry Nanostructures for Drug Delivery to the Brain
Current Medicinal Chemistry Retracted: miR-27b-3p Inhibits Invasion, Migration and Epithelial-mesenchymal Transition in Gastric Cancer by Targeting RUNX1 and Activation of the Hippo Signaling Pathway
Anti-Cancer Agents in Medicinal Chemistry The Metabolism of Anthocyanins
Current Drug Metabolism Modulation of Ischemic Brain Injury and Neuroinflammation by Adenosine A2A Receptors
Current Pharmaceutical Design New Insights into Pre-, Intra- and Post-Operative Brain Mapping in Low- Grade Glioma Surgery: Towards a Longitudinal Study of Cerebral Plasticity
Current Medical Imaging Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues
Anti-Cancer Agents in Medicinal Chemistry Novel Therapies Against Aggressive and Recurrent Epithelial Cancers by Molecular Targeting Tumor- and Metastasis-Initiating Cells and Their Progenies
Anti-Cancer Agents in Medicinal Chemistry The Interactions of the 5-HT3 Receptor with Quipazine-Like Arylpiperazine Ligands. The Journey Track at the End of the First Decade of the Third Millennium
Current Topics in Medicinal Chemistry Targeting Angiogenesis in Head and Neck Cancer
Current Cancer Drug Targets Expression, Distribution and Regulation of Phosphodiesterase 5
Current Pharmaceutical Design Receptor-Based Design of Cytokine Therapeutics
Current Pharmaceutical Biotechnology Perspectives of Fullerenes, Dendrimers, and Heterocyclic Compounds Application in Tumor Treatment
Recent Patents on Nanomedicine New Indications for Established Drugs: Combined Tumor-Stroma-Targeted Cancer Therapy with PPARγ Agonists, COX-2 Inhibitors, mTOR Antagonists and Metronomic Chemotherapy
Current Cancer Drug Targets Astrocyte Signaling and Multiple Sclerosis
Current Signal Transduction Therapy Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current Pharmaceutical Design Activation of Human Platelets by 2-Arachidonoylglycerol: Role of PKC in NO/cGMP Pathway Modulation
Current Neurovascular Research