Abstract
The TGF-β signaling pathway is central to the control of diverse biological processes including cellular proliferation, cell survival, apoptosis, extracellular matrix deposition/remodeling, migration, invasion and immune regulation/inflammation. Given the pleiotropic effects of this cytokine, it comes as no surprise that numerous pathological conditions are associated with alterations in the TGF-β pathway, including chronic fibrosis, airway remodeling (asthma), cardiovascular disease and cancer. Thus, there are increasing efforts to develop reagents and therapeutic strategies to impair TGF-β signaling. Here we review several classes of inhibitors, including knockdown strategies aimed at signaling components of the TGF-β pathway, TGF-β neutralizing antibodies, TGF-β receptor extracellular domains that function as ligand traps and small molecule kinase inhibitors. Strategies with potential for application as anti-cancer therapeutics that have been evaluated in pre-clinical animal models will be discussed. TGF-β action is complex, shifting from a tumor suppressor to a promoter of tumor cell invasion and metastasis in several types of cancer. This raises important issues regarding not only the status of the TGF-β pathway in the individual patient but also the precise stage during disease progression that such inhibitors should be employed. Potential consequences of targeting the TGF-β pathway will also be considered.
Keywords: TGF-β Pathway, antagonists, ligand-traps, knock-down strategies, kinase inhibitors, targeted therapies, pre-clinical models, cancer
Anti-Cancer Agents in Medicinal Chemistry
Title: Targeting Aberrant TGF-β Signaling in Pre-Clinical Models of Cancer
Volume: 7 Issue: 5
Author(s): Anna Alexeyevna Mourskaia, Jason Jonathan Northey and Peter Michael Siegel
Affiliation:
Keywords: TGF-β Pathway, antagonists, ligand-traps, knock-down strategies, kinase inhibitors, targeted therapies, pre-clinical models, cancer
Abstract: The TGF-β signaling pathway is central to the control of diverse biological processes including cellular proliferation, cell survival, apoptosis, extracellular matrix deposition/remodeling, migration, invasion and immune regulation/inflammation. Given the pleiotropic effects of this cytokine, it comes as no surprise that numerous pathological conditions are associated with alterations in the TGF-β pathway, including chronic fibrosis, airway remodeling (asthma), cardiovascular disease and cancer. Thus, there are increasing efforts to develop reagents and therapeutic strategies to impair TGF-β signaling. Here we review several classes of inhibitors, including knockdown strategies aimed at signaling components of the TGF-β pathway, TGF-β neutralizing antibodies, TGF-β receptor extracellular domains that function as ligand traps and small molecule kinase inhibitors. Strategies with potential for application as anti-cancer therapeutics that have been evaluated in pre-clinical animal models will be discussed. TGF-β action is complex, shifting from a tumor suppressor to a promoter of tumor cell invasion and metastasis in several types of cancer. This raises important issues regarding not only the status of the TGF-β pathway in the individual patient but also the precise stage during disease progression that such inhibitors should be employed. Potential consequences of targeting the TGF-β pathway will also be considered.
Export Options
About this article
Cite this article as:
Mourskaia Alexeyevna Anna, Northey Jonathan Jason and Siegel Michael Peter, Targeting Aberrant TGF-β Signaling in Pre-Clinical Models of Cancer, Anti-Cancer Agents in Medicinal Chemistry 2007; 7 (5) . https://dx.doi.org/10.2174/187152007781668689
DOI https://dx.doi.org/10.2174/187152007781668689 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
Exosomal MicroRNA: Diagnostic Marker and Therapeutic Tool for Lung Diseases
Current Pharmaceutical Design Pneumonia in the Elderly
Current Respiratory Medicine Reviews Bronchiolar Disorders In Childhood
Current Pediatric Reviews Endogenous Repair System of Oxidative Damage of DNA
Current Chemical Biology Gauging Reactive Metabolites in Drug-Induced Toxicity
Current Medicinal Chemistry Systemic Delivery of Peptide Hormones Using Nasal Powders: Strategies and Future Perspectives
Drug Delivery Letters Non-Injection Routes for Allergen Immunotherapy: Focus on Sublingual Immunotherapy
Inflammation & Allergy - Drug Targets (Discontinued) Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery Targeting Leukotrienes for the Treatment of COPD?
Inflammation & Allergy - Drug Targets (Discontinued) Biodiversity and Chemodiversity: Future Perspectives in Bioprospecting
Current Drug Targets Chlorine, Chlorination By-Products and Their Allergic and Respiratory Health Effects
Current Respiratory Medicine Reviews Mast Cell Tryptase β as a Target in Allergic Inflammation: An Evolving Story
Current Pharmaceutical Design Epidemiology and Pathophysiology of Chronic Cough
Current Respiratory Medicine Reviews Lipid Rafts and Fas/CD95 Signaling in Cancer Chemotherapy
Recent Patents on Anti-Cancer Drug Discovery Anti-TNF Treatment in Rheumatoid Arthritis
Current Pharmaceutical Design Cholestasis During Pregnancy: Aetiopathogenesis, Foetal-Maternal Repercussions and Pharmacological Treatments
Current Women`s Health Reviews In-person vs. eHealth Mindfulness-based Intervention for Adolescents with Chronic Illnesses: A Pilot Randomized Trial
Adolescent Psychiatry Cellular and Subcellular Imaging in Live Mice Using Fluorescent Proteins
Current Pharmaceutical Biotechnology Structure-Based Rational Design of Adenosine Receptor Ligands
Current Topics in Medicinal Chemistry Circulating MicroRNAs as a New Class of Biomarkers of Physiological Reactions of the Organism to the Intake of Dietary Supplements and Drugs
MicroRNA