Abstract
Autophagy, an intracellular process involved in removing and recycling cellular components, plays a major role in growth, development, and responses to stress and pathogens. Autophagy is compromised in many human diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Autophagy malfunction is associated to an alteration of both innate and adaptative immune responses, defects in bacterial clearance, and malfunction of goblet and Paneth cells; all these perturbations are related to IBD and CRC pathogenesis. Preclinical data show that both inhibition and induction of autophagy have significant potential to be translated into the clinic. Inhibitors of TORC1 (rapamycin and rapalogs) have proven to be effective in IBD and in many models for CRCs; however, their clinical use has produced only modest success. Second generations of mTOR inhibitors, which target its kinase domain, have been more effective. Optimal antitumor efficacy is achieved by combination of agents with different molecular targets, such as proteasome or histone deacetylase inhibitors combined with autophagy inhibitors (hydroxychloroquine) or activators (everolimus). Clinical trials in course are assaying the effect of these compounds in combination with standard treatments of CRC. This review summarizes current knowledge about the autophagic machinery and its regulation, then it explores the relevance and impact of the malfunction of autophagy on the pathogenesis of IBD and CRC, and, finally, it discusses the therapeutic potential of molecules that regulate autophagy and their use for the treatment of these two diseases.
Keywords: AMP-dependent kinase, autophagy, colorectal cancer, Endoplasmic Reticulum stress, inflammatory bowel disease, mammalian target of rapamycin, cellular components, Paneth cells, mTOR inhibitors, proteasome.
Current Pharmaceutical Design
Title:Pharmacological Control of Autophagy: Therapeutic Perspectives in Inflammatory Bowel Disease and Colorectal Cancer
Volume: 18 Issue: 26
Author(s): Sofia Garcia-Maurino, Antonio Alcaide and Cecilia Dominguez
Affiliation:
Keywords: AMP-dependent kinase, autophagy, colorectal cancer, Endoplasmic Reticulum stress, inflammatory bowel disease, mammalian target of rapamycin, cellular components, Paneth cells, mTOR inhibitors, proteasome.
Abstract: Autophagy, an intracellular process involved in removing and recycling cellular components, plays a major role in growth, development, and responses to stress and pathogens. Autophagy is compromised in many human diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Autophagy malfunction is associated to an alteration of both innate and adaptative immune responses, defects in bacterial clearance, and malfunction of goblet and Paneth cells; all these perturbations are related to IBD and CRC pathogenesis. Preclinical data show that both inhibition and induction of autophagy have significant potential to be translated into the clinic. Inhibitors of TORC1 (rapamycin and rapalogs) have proven to be effective in IBD and in many models for CRCs; however, their clinical use has produced only modest success. Second generations of mTOR inhibitors, which target its kinase domain, have been more effective. Optimal antitumor efficacy is achieved by combination of agents with different molecular targets, such as proteasome or histone deacetylase inhibitors combined with autophagy inhibitors (hydroxychloroquine) or activators (everolimus). Clinical trials in course are assaying the effect of these compounds in combination with standard treatments of CRC. This review summarizes current knowledge about the autophagic machinery and its regulation, then it explores the relevance and impact of the malfunction of autophagy on the pathogenesis of IBD and CRC, and, finally, it discusses the therapeutic potential of molecules that regulate autophagy and their use for the treatment of these two diseases.
Export Options
About this article
Cite this article as:
Garcia-Maurino Sofia, Alcaide Antonio and Dominguez Cecilia, Pharmacological Control of Autophagy: Therapeutic Perspectives in Inflammatory Bowel Disease and Colorectal Cancer, Current Pharmaceutical Design 2012; 18 (26) . https://dx.doi.org/10.2174/138161212802083653
DOI https://dx.doi.org/10.2174/138161212802083653 |
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
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
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Critical Steps in Tissue Processing in Histopathology
Recent Patents on DNA & Gene Sequences Stromal Cell-Derived Factor (SDF) 2 and the Endoplasmic Reticulum Stress Response of Trophoblast Cells in Gestational Diabetes Mellitus and <i>In vitro</i> Hyperglycaemic Condition
Current Vascular Pharmacology Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery 177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma
Current Radiopharmaceuticals Progranulin Regulates Inflammation and Tumor
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Inventions Designed to Enhance Drug Delivery Across Epithelial and Endothelial Cells Through the Paracellular Pathway
Recent Patents on Drug Delivery & Formulation Superheated Water as Solvent in Microwave Assisted Organic Synthesis of Compounds of Valuable Pharmaceutical Interest
Current Organic Chemistry Molecular Bases of Liver Cancer Refractoriness to Pharmacological Treatment
Current Medicinal Chemistry Potential Role of MEK Inhibition in Treating Patients with Colorectal Cancer
Current Cancer Therapy Reviews MicroRNAs and Lung Cancer: New Oncogenes and Tumor Suppressors, New Prognostic Factors and Potential Therapeutic Targets
Current Medicinal Chemistry Protective Effect of Annurca Apple Extract Against Oxidative Damage in Human Erythrocytes
Current Nutrition & Food Science Regulation of Autophagy in Oxygen-Dependent Cellular Stress
Current Pharmaceutical Design Reversing Aberrant Methylation Patterns in Cancer
Current Medicinal Chemistry Proline-Directed Protein Kinase FA as a Potential Target for Diagnosis and Therapy of Human Cancers
Current Cancer Drug Targets Role of CD73 in Disease: Promising Prognostic Indicator and Therapeutic Target
Current Medicinal Chemistry Epidemiology of Upper Gastrointestinal Damage Associated with Low-Dose Aspirin
Current Pharmaceutical Design Inhibition of Glycolysis and Glutaminolysis: An Emerging Drug Discovery Approach to Combat Cancer
Current Topics in Medicinal Chemistry All for Statins and Statins for All; An Update
Current Pharmaceutical Design The Role of the Gastrointestinal Microbiota in Colorectal Cancer
Current Pharmaceutical Design Expression of CDK8 and CDK8-interacting Genes as Potential Biomarkers in Breast Cancer
Current Cancer Drug Targets