Abstract
Despite impressive treatment advances, few options for refractory or relapsed Hodgkin Lymphoma (HL) are available and there is a need for new compounds development. A number of promising agents with multiple mechanisms of action are under investigation. Microenvironment and neoangiogenesis are acquiring a rising relevance in the pathophysiology and progression of HL. Everolimus (RAD001) is an oral antineoplastic agent derived from rapamycin, a macrocyclic lactone antibiotic, targeting the mammalian target of rapamycin (mTOR). Although the importance of mTOR signaling in the deregulated cell growth of human neoplastic cells has been recognized, this pathway is also emerging as a key regulator of the tumor response to hypoxia, as well as endothelial and stromal cells function, thereby regulating neoangiogenesis. Furthermore, mTOR plays an important role in anticancer drug resistance. The actions of everolimus within the mTOR pathway in HL result in decreased protein synthesis and cell cycle arrest, as well as in decreased angiogenesis. Everolimus has shown preliminary evidence of efficacy as a single-agent in heavily pretreated relapsed/refractory HL, with an overall fair safety profile. The purpose of this review is to discuss the employment of everolimus as an antiproliferative and antiangiogenic agent in HL and to report the critical role of the mTOR pathway and angiogenesis in this malignancy.
Keywords: Everolimus, refractory Hodgkin Lymphoma, relapsed Hodgkin Lymphoma, mTOR inhibitors, mTORC1, microenvironment, angiogenesis, microvessel density, HIF-1a, VEGF, PI3K/Akt pathway, Hodgkin Lymphoma progression, Hodgkin Lymphoma pathogenesis, stromal cells
Current Medicinal Chemistry
Title: mTOR as a Target of Everolimus in Refractory/Relapsed Hodgkin Lymphoma
Volume: 19 Issue: 7
Author(s): A. Guarini, C. Minoia, M. Giannoccaro, A. Rana, A. Iacobazzi, A. Lapietra, A. Raimondi, N. Silvestris, C. D. Gadaleta and G. Ranieri
Affiliation:
Keywords: Everolimus, refractory Hodgkin Lymphoma, relapsed Hodgkin Lymphoma, mTOR inhibitors, mTORC1, microenvironment, angiogenesis, microvessel density, HIF-1a, VEGF, PI3K/Akt pathway, Hodgkin Lymphoma progression, Hodgkin Lymphoma pathogenesis, stromal cells
Abstract: Despite impressive treatment advances, few options for refractory or relapsed Hodgkin Lymphoma (HL) are available and there is a need for new compounds development. A number of promising agents with multiple mechanisms of action are under investigation. Microenvironment and neoangiogenesis are acquiring a rising relevance in the pathophysiology and progression of HL. Everolimus (RAD001) is an oral antineoplastic agent derived from rapamycin, a macrocyclic lactone antibiotic, targeting the mammalian target of rapamycin (mTOR). Although the importance of mTOR signaling in the deregulated cell growth of human neoplastic cells has been recognized, this pathway is also emerging as a key regulator of the tumor response to hypoxia, as well as endothelial and stromal cells function, thereby regulating neoangiogenesis. Furthermore, mTOR plays an important role in anticancer drug resistance. The actions of everolimus within the mTOR pathway in HL result in decreased protein synthesis and cell cycle arrest, as well as in decreased angiogenesis. Everolimus has shown preliminary evidence of efficacy as a single-agent in heavily pretreated relapsed/refractory HL, with an overall fair safety profile. The purpose of this review is to discuss the employment of everolimus as an antiproliferative and antiangiogenic agent in HL and to report the critical role of the mTOR pathway and angiogenesis in this malignancy.
Export Options
About this article
Cite this article as:
Guarini A., Minoia C., Giannoccaro M., Rana A., Iacobazzi A., Lapietra A., Raimondi A., Silvestris N., D. Gadaleta C. and Ranieri G., mTOR as a Target of Everolimus in Refractory/Relapsed Hodgkin Lymphoma, Current Medicinal Chemistry 2012; 19 (7) . https://dx.doi.org/10.2174/092986712799320727
DOI https://dx.doi.org/10.2174/092986712799320727 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Recent Progress in the Development of Quinoline Derivatives for the Exploitation of Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Impact of Epigenetic Dietary Components on Cancer through Histone Modifications
Current Medicinal Chemistry Targeting Key Transporters in Tumor Glycolysis as a Novel Anticancer Strategy
Current Topics in Medicinal Chemistry New Mechanistic Insight on the PIM-1 Kinase Inhibitor AZD1208 Using Multidrug Resistant Human Erythroleukemia Cell Lines and Molecular Docking Simulations
Current Topics in Medicinal Chemistry Plant Derived Inhibitor Sulforaphane in Combinatorial Therapy Against Therapeutically Challenging Pancreatic Cancer
Anti-Cancer Agents in Medicinal Chemistry Caspases: Structure-Guided Design of Drugs to Control Cell Death
Mini-Reviews in Medicinal Chemistry Synthesis and Biological Evaluation of a Novel Apogossypolone Derivative
Letters in Drug Design & Discovery Synthesis and in vitro Evaluation of the Anticancer Potential of New Aminoalkanol Derivatives of Xanthone
Anti-Cancer Agents in Medicinal Chemistry Crocin Protects Against Beta-Amyloid Peptide-Induced Apoptosis in PC12 Cells Via the PI3 K Pathway
Current Molecular Pharmacology Emerging Concepts for the Treatment of Hematological Malignancies with Therapeutic Monoclonal Antibodies
Current Drug Targets Endocannabinoid System: A Promising Therapeutic Target for the Treatment of Haematological Malignancies?
Current Medicinal Chemistry The Intermediate Enzymes of Isoprenoid Metabolism as Anticancer Targets
Anti-Cancer Agents in Medicinal Chemistry Design of Self-Immolative Linkers for Tumour-Activated Prodrug Therapy
Anti-Cancer Agents in Medicinal Chemistry Novel Imaging Techniques in Acute Kidney Injury
Current Drug Targets Mitochondrial Superoxide Dismutase - Signals of Distinction
Anti-Cancer Agents in Medicinal Chemistry Functional and Clinical Significance of the Integrin Alpha Chain CD49d Expression in Chronic Lymphocytic Leukemia
Current Cancer Drug Targets E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets
Current Cancer Drug Targets Dasabuvir: A Non-Nucleoside Inhibitor of NS5B for the Treatment of Hepatitis C Virus Infection
Reviews on Recent Clinical Trials Targeting the Cancer Biomarker CD47: A Review on the Diverse Mechanisms of the CD47 Pathway in Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Novel Patents and Cancer Therapies for Transforming Growth Factor- Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis
Recent Patents on Anti-Cancer Drug Discovery