Abstract
Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative “smart drugs”. The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.
Keywords: Bone, Bone resorption, Cancer, Cathepsin K, CXCR4, Denosumab, ETAR, Metastasis, Molecular Targeted Therapy, Osteoclasts, Pain, RANKL, Skeletal Related Events, Src
Current Medicinal Chemistry
Title: Bone Metastatic Disease: Taking Aim at New Therapeutic Targets
Volume: 18 Issue: 20
Author(s): F. Coluzzi, E. Di Bussolo, I. Mandatori and C. Mattia
Affiliation:
Keywords: Bone, Bone resorption, Cancer, Cathepsin K, CXCR4, Denosumab, ETAR, Metastasis, Molecular Targeted Therapy, Osteoclasts, Pain, RANKL, Skeletal Related Events, Src
Abstract: Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative “smart drugs”. The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.
Export Options
About this article
Cite this article as:
Coluzzi F., Di Bussolo E., Mandatori I. and Mattia C., Bone Metastatic Disease: Taking Aim at New Therapeutic Targets, Current Medicinal Chemistry 2011; 18 (20) . https://dx.doi.org/10.2174/092986711796391660
DOI https://dx.doi.org/10.2174/092986711796391660 |
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
-
Renal Neoplasia in the Hyperparathyroidism-Jaw Tumor Syndrome
Current Molecular Medicine Vitamin D and the Adaptive Immune System with Special Emphasis to Allergic Reactions and Allograft Rejection
Inflammation & Allergy - Drug Targets (Discontinued) Vitamin D and Vascular Disease
Current Vascular Pharmacology Endocrine Therapy of Breast Cancer
Current Medicinal Chemistry From Pituitary Adenoma to Pituitary Neuroendocrine Tumors: How Molecular Pathways may Impact the Therapeutic Management?
Endocrine, Metabolic & Immune Disorders - Drug Targets Pharmacologic Role of Vitamin D Natural Products
Current Vascular Pharmacology Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration
Current Pharmaceutical Design Micronutrients at the Interface Between Inflammation and Infection Ascorbic Acid and Calciferol. Part 2: Calciferol and the Significance of Nutrient Supplements
Inflammation & Allergy - Drug Targets (Discontinued) Strategies to Convert PACAP from a Hypophysiotropic Neurohormone Into a Neuroprotective Drug
Current Pharmaceutical Design CIAPIN1 siRNA Inhibits Proliferation, Migration and Promotes Apoptosis of VSMCs by Regulating Bcl-2 and Bax
Current Neurovascular Research Modulation of Energy Intake and Expenditure Due to Habitual Physical Exercise
Current Pharmaceutical Design Medications Affecting Functional Status in Older Persons
Current Pharmaceutical Design Methods for Biomarker Verification and Assay Development
Current Proteomics Open Questions on Bioequivalence: An Updated Reappraisal
Current Clinical Pharmacology Metastatic Breast Cancer, Organotropism and Therapeutics: A Review
Current Cancer Drug Targets Strategies that Target Tight Junctions for Enhanced Drug Delivery
Current Pharmaceutical Design The Roles of Parathyroid Hormone and Calcitonin in Bone Remodeling: Prospects for Novel Therapeutics
Endocrine, Metabolic & Immune Disorders - Drug Targets Vitamin D and Cardiovascular Disease: A Novel Agent for Reducing Cardiovascular Risk?
Current Vascular Pharmacology Targeted Therapy Options for Treatment of Bone Metastases; Beyond Bisphosphonates
Current Pharmaceutical Design Bioaccessibility of Functional Ingredients
Current Nutrition & Food Science