Abstract
Retinoic acid and natural as well as synthetic derivatives (retinoids) are promising anti-neoplastic agents endowed with both therapeutic and chemopreventive potential. Although the treatment of acute promyelocic leukemia with all-trans retinoic acid is an outstanding example, the full potential of retinoids in oncology has not yet been exploited and a more generalized use of these compounds is not yet a reality. This may be the result of issues such as natural and induced resistance as well as local and systemic toxicity. One way to enhance the therapeutic and chemopreventive activity of retinoic acid and derivatives is to identify rational combinations between these compounds and other pharmacological agents. This is now possible given the wealth of information available on the biochemical and molecular mechanisms underlying the biological activity of retinoids. At the cellular level, the anti-leukemia and anti-cancer activity of retinoids is the result of three main actions, cell-differentiation, growth inhibition and apoptosis. At the molecular level, retinoids act through the activation of nuclear-retinoic-acid-receptor-dependent and-independent pathways. The cellular pathways and molecular networks relevant for retinoid activity are modulated by a panoply of other intra-cellular and extra-cellular pathways that may be targeted by known drugs and other experimental therapeutics. The review article aims to summarize and critically discuss the available knowledge in the field and provide a rational framework that may be useful for the design of effective drug combinations with the potential to enhance the therapeutic index of retinoids.
Keywords: all-trans retinoic acid, acute myeloid leukemia, RXR agonists, Neuroblastoma, Hedgehog pathway
Current Pharmaceutical Design
Title: Retinoids as Differentiating Agents in Oncology: A Network of Interactions with Intracellular Pathways as the Basis for Rational Therapeutic Combinations
Volume: 13 Issue: 13
Author(s): Enrico Garattini, Maurizio Gianni and Mineko Terao
Affiliation:
Keywords: all-trans retinoic acid, acute myeloid leukemia, RXR agonists, Neuroblastoma, Hedgehog pathway
Abstract: Retinoic acid and natural as well as synthetic derivatives (retinoids) are promising anti-neoplastic agents endowed with both therapeutic and chemopreventive potential. Although the treatment of acute promyelocic leukemia with all-trans retinoic acid is an outstanding example, the full potential of retinoids in oncology has not yet been exploited and a more generalized use of these compounds is not yet a reality. This may be the result of issues such as natural and induced resistance as well as local and systemic toxicity. One way to enhance the therapeutic and chemopreventive activity of retinoic acid and derivatives is to identify rational combinations between these compounds and other pharmacological agents. This is now possible given the wealth of information available on the biochemical and molecular mechanisms underlying the biological activity of retinoids. At the cellular level, the anti-leukemia and anti-cancer activity of retinoids is the result of three main actions, cell-differentiation, growth inhibition and apoptosis. At the molecular level, retinoids act through the activation of nuclear-retinoic-acid-receptor-dependent and-independent pathways. The cellular pathways and molecular networks relevant for retinoid activity are modulated by a panoply of other intra-cellular and extra-cellular pathways that may be targeted by known drugs and other experimental therapeutics. The review article aims to summarize and critically discuss the available knowledge in the field and provide a rational framework that may be useful for the design of effective drug combinations with the potential to enhance the therapeutic index of retinoids.
Export Options
About this article
Cite this article as:
Garattini Enrico, Gianni Maurizio and Terao Mineko, Retinoids as Differentiating Agents in Oncology: A Network of Interactions with Intracellular Pathways as the Basis for Rational Therapeutic Combinations, Current Pharmaceutical Design 2007; 13 (13) . https://dx.doi.org/10.2174/138161207780618786
DOI https://dx.doi.org/10.2174/138161207780618786 |
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
-
Interaction of ABC Multidrug Transporters with Anticancer Protein Kinase Inhibitors: Substrates and/or Inhibitors?
Current Cancer Drug Targets The Intracellular Domain of Amyloid Precursor Protein is a Potential Therapeutic Target in Alzheimer’s Disease
Current Drug Discovery Technologies Astrocytes as a 5-HT2B-Mediated SERT-Independent SSRI Target, Slowly Altering Depression-Associated Genes and Function
Current Signal Transduction Therapy Synthesis and Biological Evaluation of Licofelone Derivatives as Anticancer and Anti-inflammatory Agents
Letters in Drug Design & Discovery Changing the Endocrine Dependence of Breast Cancer: Data and Hypotheses
Current Medicinal Chemistry Cancer Drug Discovery Targeting Histone Methyltransferases: An Update
Current Medicinal Chemistry Selected Approaches for Rational Drug Design and High Throughput Screening to Identify Anti-Cancer Molecules
Anti-Cancer Agents in Medicinal Chemistry Matrix Metalloproteinases
Current Medicinal Chemistry Vitamin D - Pivotal Nutraceutical in the Regulation of Cancer Metastasis and Angiogenesis
Current Medicinal Chemistry Advances Towards The Discovery of GPR55 Ligands
Current Medicinal Chemistry Mycotherapy of Cancer: An Update on Cytotoxic and Antitumor Activities of Mushrooms, Bioactive Principles and Molecular Mechanisms of their Action
Current Topics in Medicinal Chemistry Small Molecule Ligands of the Human Melanocortin-4 Receptor
Current Topics in Medicinal Chemistry The Role of DNA Methylation in the Pathogenesis and Treatment of Cancer
Current Clinical Pharmacology The Inhibition of Cell Proliferation Using Silencing of N-Cadherin Gene by siRNA Process in Human Melanoma Cell Lines
Current Medicinal Chemistry Protein Kinases and their Modulation in the Central Nervous System
Current Medicinal Chemistry - Central Nervous System Agents COX-2 Inhibition in Esophagitis, Barretts Esophagus and Esophageal Cancer
Current Pharmaceutical Design Ca<sup>2+</sup> Signalling in Endothelial Progenitor Cells: A Novel Means to Improve Cell-Based Therapy and Impair Tumour Vascularisation
Current Vascular Pharmacology Statins as Either Immunomodulators or Anti-Cancer Drugs: Functional Activities on Tumor Stromal Cells and Natural Killer Cells
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Pyrazole Substituted 9-Anilinoacridines as HER2 Inhibitors Targeting Breast Cancer - An <i>in-silico</i> approach
Current Drug Research Reviews Cysteine Network (CYSTEINET) Dysregulation in Parkinson’s Disease: Role of N-acetylcysteine
Current Drug Metabolism