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Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling
Joint Authors
Bolzoni, Marina
Accardi, Fabrizio
Toscani, Denise
Dalla Palma, Benedetta
Aversa, Franco
Giuliani, Nicola
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-10-22
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Multiple myeloma (MM) is characterized by a high capacity to induce alterations in the bone remodeling process.
The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM.
The proteasome inhibitor (PI) bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome.
However, recently novel PIs have been developed to overcome bortezomib resistance.
Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation.
It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) or stimulates the osteoblast differentiation.
Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation.
In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers.
In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number.
This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease.
American Psychological Association (APA)
Accardi, Fabrizio& Toscani, Denise& Bolzoni, Marina& Dalla Palma, Benedetta& Aversa, Franco& Giuliani, Nicola. 2015. Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling. BioMed Research International،Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1054490
Modern Language Association (MLA)
Accardi, Fabrizio…[et al.]. Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling. BioMed Research International No. 2015 (2015), pp.1-13.
https://search.emarefa.net/detail/BIM-1054490
American Medical Association (AMA)
Accardi, Fabrizio& Toscani, Denise& Bolzoni, Marina& Dalla Palma, Benedetta& Aversa, Franco& Giuliani, Nicola. Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1054490
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1054490