Challenging the current approaches to multiple myeloma-related bone disease: from bisphosphonates to target therapy.
Bone disease (BD) is the hall-mark clinical feature of multiple myeloma (MM), accounting up to 60% of patients with bone pain at diagnosis and 60% with a pathologic fracture during the course of their disease. Experimental models, which recapitulate in vivo the human bone marrow microenvironment (HBMM) in immunodeficient mice have been recently developed as valuable tool for the study of MM pathophysiology as well as the experimental treatment of BD. At present, bisphosphonates are the mainstay treatment of MM-related BD. The growing information on the cellular and molecular bases of BD as well as the availability of novel anti-resorptive agents, such as the IgG1-anti-RANKL (AMG 161) Denosumab, are now depicting a new scenario where the treatment will be afforded by the use of different agents. Furthermore the availability of highthroughput molecular profiling approaches, including DNA microarrays and proteomics, is likely to provide new platforms for patients stratification and treatment individualization on specific targets. It is now the right time for a therapeutical approach which is rationally based on the complexity of the biopathology of MM-related BD.
Tassone
P
P
Medical Oncology Unit and Center for Innovative Treatments in Medical Oncology, University of Magna Graecia and Tommaso Campanella Cancer Center, Catanzaro 88100, Italy. tassone@unicz.it
Tagliaferri
P
P
Rossi
M
M
Calimeri
T
T
Bulotta
A
A
Abbruzzese
A
A
Caraglia
M
M
Neri
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D004164:Diphosphonates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D009101:Multiple Myeloma / Q000188:drug therapy*; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates