RANK ligand as a therapeutic target for bone metastases and multiple myeloma

G. David Roodman, William C. Dougall

Research output: Contribution to journalReview article

86 Scopus citations

Abstract

Osteoclastic bone resorption is a critical component of skeletal complications of malignancy including fracture, bone pain, hypercalcemia, and spinal cord compression. Three proteins, RANKL, RANK, and OPG have been recently identified as key determinants of osteoclastogenesis and the regulation of bone resorption. Both RANKL and OPG can be aberrantly regulated in the cancer setting and function as important gatekeepers of tumor-induced osteolytic bone disease. RANKL-induced osteoclastogenesis not only mediates osteolytic bone disease, but also contributes to the pathogenesis of osteoblastic bone disease resulting from tumors. In addition, an important role was recently described for bone marrow derived RANKL to mediate the bone-specific tropism of RANK-expressing tumor cells. This manuscript will review how RANKL contributes to skeletal complications of cancer and the development of targeted, mechanism-based drugs that inhibit RANKL.

Original languageEnglish (US)
Pages (from-to)92-101
Number of pages10
JournalCancer Treatment Reviews
Volume34
Issue number1
DOIs
StatePublished - Feb 1 2008

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Keywords

  • Bone metastasis
  • Breast cancer
  • Multiple myeloma
  • OPG
  • Osteoclast
  • Prostate cancer
  • RANK
  • RANKL
  • Skeletal complications

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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