Clinical development of anti-RANKL therapies for treatment and prevention of bone metastasis

Allan Lipton, Carsten Goessl

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

The clinical sequelae from bone metastases, termed skeletal-related events, are among the most frequent and debilitating complications in patients with advanced cancer. Bone metastases are characterized by pathologically increased osteoclast activity, and accumulating evidence indicates that tumor cells interact within the bone to stimulate the RANK-RANK ligand (RANKL) pathway. RANKL is an essential mediator of osteoclast formation, function, and survival. Because of the central role of RANKL in cancer-induced bone destruction, the inhibition of RANKL has the potential to result in the reduction of pathologic bone resorption. Denosumab is a fully human monoclonal antibody specific for RANKL that inhibits the formation, activation, and survival of osteoclasts. This in turn decreases bone resorption and reduces cancer-induced bone destruction. As a result of its unique and specific mechanism of action, denosumab is being investigated for use in patients with advanced malignancies involving bone to prevent the occurrence of skeletal-related events.

Original languageEnglish (US)
Pages (from-to)96-99
Number of pages4
JournalBone
Volume48
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

RANK Ligand
Neoplasm Metastasis
Bone and Bones
Osteoclasts
Bone Neoplasms
Bone Resorption
Therapeutics
Neoplasms
Monoclonal Antibodies
Survival

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

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abstract = "The clinical sequelae from bone metastases, termed skeletal-related events, are among the most frequent and debilitating complications in patients with advanced cancer. Bone metastases are characterized by pathologically increased osteoclast activity, and accumulating evidence indicates that tumor cells interact within the bone to stimulate the RANK-RANK ligand (RANKL) pathway. RANKL is an essential mediator of osteoclast formation, function, and survival. Because of the central role of RANKL in cancer-induced bone destruction, the inhibition of RANKL has the potential to result in the reduction of pathologic bone resorption. Denosumab is a fully human monoclonal antibody specific for RANKL that inhibits the formation, activation, and survival of osteoclasts. This in turn decreases bone resorption and reduces cancer-induced bone destruction. As a result of its unique and specific mechanism of action, denosumab is being investigated for use in patients with advanced malignancies involving bone to prevent the occurrence of skeletal-related events.",
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Clinical development of anti-RANKL therapies for treatment and prevention of bone metastasis. / Lipton, Allan; Goessl, Carsten.

In: Bone, Vol. 48, No. 1, 01.01.2011, p. 96-99.

Research output: Contribution to journalReview article

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