The Role of Proteasome Inhibitors in Multiple Myeloma Bone Disease and Bone Metastasis: Effects on Osteoblasts and Osteocytes
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TLDR
PIs have been recently proven to also be efficacious in blocking MM-induced osteocyte death providing new possible therapeutic use in the management of bone loss, and the conjugation of PIs with bisphosphonates showed good results in terms of bone anabolic activity.Abstract:
The alterations of bone remodeling are typical of multiple myeloma (MM) patients where the uncoupled and unbalanced bone remodeling caused the onset of osteolytic lesions. Moreover, bone metastasis occurs in the majority of patients with breast and prostate cancer. Skeletal-related events negatively impact on quality of life by increasing the vulnerability to fractures. Several bone-targeting treatments have been developed to control bone pain and pathological fractures, including bisphosphonates and Denosumab. Nevertheless, these agents act by inhibiting osteoclast activity but do not improve bone formation. Proteasome inhibitors (PIs) have shown bone anabolic effects and encouraging results in stimulating osteoblast differentiation and bone healing. Among these, the first-in-class bortezomib and the second-generation PIs, carfilzomib, and ixazomib regulate the bone remodeling process by controlling the degradation of several bone proteins. PIs have been recently proven to also be efficacious in blocking MM-induced osteocyte death providing new possible therapeutic use in the management of bone loss. PIs have significant side effects that limit their use as bone anabolic strategy. Multiple alternative approaches have been made. The conjugation of PIs with bisphosphonates, which can target them to bone, showed good results in terms of bone anabolic activity. However, the clinical implications of these effects require further investigations.read more
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Mechanisms, Diagnosis and Treatment of Bone Metastases
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References
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Journal ArticleDOI
A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes.
Marci D. Jones,Julie C. Liu,Thomas K. Barthel,Sadiq Hussain,Erik Lovria,Dengfeng Cheng,Jesse Schoonmaker,Sudhanshu Mulay,David C. Ayers,Mary L. Bouxsein,Gary S. Stein,Siddhartha Mukherjee,Jane B. Lian +12 more
TL;DR: In vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone.
Journal ArticleDOI
Bone Marrow Monocyte / Macrophage Derived Activin A Mediates the Osteoclastogenic Effect of IL-3 in Multiple Myeloma
Rebecca Silbermann,Marina Bolzoni,Paola Storti,Daniela Guasco,Sabrina Bonomini,Dan Zhou,Jingwei Wu,Judith L. Anderson,Jolene J. Windle,Franco Aversa,G. David Roodman,G. David Roodman,Nicola Giuliani +12 more
TL;DR: Bone marrow monocyte-/macrophage-derived activin A mediates the osteoclastogenic effect of IL-3 in multiple myeloma.
Journal ArticleDOI
A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients
Maurizio Zangari,Shmuel Yaccoby,Lisa Pappas,Federica Cavallo,Naveen Sanath Kumar,Ranganathan S,Larry J. Suva,Gruenwald Jm,Kern S,Fenghuang Zhan,Dixie-Lee Esseltine,Guido Tricot +11 more
TL;DR: It is demonstrated that the myeloma control produced by proteasome inhibition is associated with bone changes and to a discrete pattern of hormonal variation.
Journal ArticleDOI
The Proteasome Inhibitor Bortezomib Maintains Osteocyte Viability in Multiple Myeloma Patients by Reducing Both Apoptosis and Autophagy: A New Function for Proteasome Inhibitors.
Denise Toscani,Carla Palumbo,Benedetta Dalla Palma,Marzia Ferretti,Marina Bolzoni,Valentina Marchica,Paola Sena,Eugenia Martella,Cristina Mancini,Valentina Ferri,Federica Costa,Fabrizio Accardi,Luisa Craviotto,Franco Aversa,Nicola Giuliani +14 more
TL;DR: Osteocyte autophagy is identified as a new potential target in MM bone disease and the use of PIs to maintain osteocyte viability and improve bone integrity in MM patients is supported.
Journal ArticleDOI
Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20
B Dalla Palma,Daniela Guasco,Mario Pedrazzoni,Marina Bolzoni,Fabrizio Accardi,Federica Costa,Gabriella Sammarelli,Luisa Craviotto,M. De Filippo,Livia Ruffini,Paola Omedè,Roberto Ria,Franco Aversa,Nicola Giuliani +13 more
TL;DR: The relationship between bone disease and the BM cytokine and chemokine patterns highlighting the tight relationship between CCL20 BM levels and osteolysis in multiple myeloma patients is defined.