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Denosumab: a new option in the treatment of bone metastases from urological cancers

Bone metastases often create serious clinical problems: they lead to poor performance status due to pathologic fractures, spinal cord compression and intractable pain, commonly referred to as skeletal-related events. The receptor activator of nuclear factor-κB (RANK), the RANK ligand (RANKL), and os...

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Autores principales: Yuasa, Takeshi, Yamamoto, Shinya, Urakami, Shinji, Fukui, Iwao, Yonese, Junji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457675/
https://www.ncbi.nlm.nih.gov/pubmed/23055747
http://dx.doi.org/10.2147/OTT.S30578
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author Yuasa, Takeshi
Yamamoto, Shinya
Urakami, Shinji
Fukui, Iwao
Yonese, Junji
author_facet Yuasa, Takeshi
Yamamoto, Shinya
Urakami, Shinji
Fukui, Iwao
Yonese, Junji
author_sort Yuasa, Takeshi
collection PubMed
description Bone metastases often create serious clinical problems: they lead to poor performance status due to pathologic fractures, spinal cord compression and intractable pain, commonly referred to as skeletal-related events. The receptor activator of nuclear factor-κB (RANK), the RANK ligand (RANKL), and osteoprotegerin, a decoy receptor for RANK, regulate osteoclastogenesis and may play a key role in bone metastasis. Denosumab (XGEVA; Amgen, Thousand Oaks, CA), a fully human monoclonal antibody that binds to and neutralizes RANKL, inhibits osteoclast function, prevents generalized bone resorption and local bone destruction, and has become a therapeutic option for preventing or delaying first on-study skeletal-related events in various malignancies. In the context of urological cancer, three main Phase III clinical studies have been published in prostate cancer. This article provides a brief overview of the characteristics of bone metastasis in urological cancers, reviews the mechanisms of bone metastasis, including the RANK/RANKL/osteoprotegerin axis, the current standard of care, zoledronic acid, and describes the efficacy of the novel bone-targeted agent denosumab in bone metastasis. Denosumab is emerging as a key therapeutic option in the treatment of bone metastases from urological cancers.
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spelling pubmed-34576752012-10-09 Denosumab: a new option in the treatment of bone metastases from urological cancers Yuasa, Takeshi Yamamoto, Shinya Urakami, Shinji Fukui, Iwao Yonese, Junji Onco Targets Ther Review Bone metastases often create serious clinical problems: they lead to poor performance status due to pathologic fractures, spinal cord compression and intractable pain, commonly referred to as skeletal-related events. The receptor activator of nuclear factor-κB (RANK), the RANK ligand (RANKL), and osteoprotegerin, a decoy receptor for RANK, regulate osteoclastogenesis and may play a key role in bone metastasis. Denosumab (XGEVA; Amgen, Thousand Oaks, CA), a fully human monoclonal antibody that binds to and neutralizes RANKL, inhibits osteoclast function, prevents generalized bone resorption and local bone destruction, and has become a therapeutic option for preventing or delaying first on-study skeletal-related events in various malignancies. In the context of urological cancer, three main Phase III clinical studies have been published in prostate cancer. This article provides a brief overview of the characteristics of bone metastasis in urological cancers, reviews the mechanisms of bone metastasis, including the RANK/RANKL/osteoprotegerin axis, the current standard of care, zoledronic acid, and describes the efficacy of the novel bone-targeted agent denosumab in bone metastasis. Denosumab is emerging as a key therapeutic option in the treatment of bone metastases from urological cancers. Dove Medical Press 2012-09-21 /pmc/articles/PMC3457675/ /pubmed/23055747 http://dx.doi.org/10.2147/OTT.S30578 Text en © 2012 Yuasa et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Review
Yuasa, Takeshi
Yamamoto, Shinya
Urakami, Shinji
Fukui, Iwao
Yonese, Junji
Denosumab: a new option in the treatment of bone metastases from urological cancers
title Denosumab: a new option in the treatment of bone metastases from urological cancers
title_full Denosumab: a new option in the treatment of bone metastases from urological cancers
title_fullStr Denosumab: a new option in the treatment of bone metastases from urological cancers
title_full_unstemmed Denosumab: a new option in the treatment of bone metastases from urological cancers
title_short Denosumab: a new option in the treatment of bone metastases from urological cancers
title_sort denosumab: a new option in the treatment of bone metastases from urological cancers
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457675/
https://www.ncbi.nlm.nih.gov/pubmed/23055747
http://dx.doi.org/10.2147/OTT.S30578
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