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

BioMed Research International

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

Medicine

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