Skeletal metastases: Decreasing tumor burden by targeting the bone microenvironment

Research output: Contribution to journalReview article

30 Scopus citations

Abstract

Several common cancers often metastasize to the skeleton in advanced disease. Bone metastases are incurahle and cause protracted, severe symptoms. Growth of tumor in bone is driven by a vicious cycle: tumor-secreted factors stimulate bone cells, which in turn release growth factors and cytokines. The bone-derived factors fuel the vicious cycle by acting back on the tumor cells. The vicious cycle offers novel targets for the treatment of advanced cancers. Treatments can inhibit bone cells (osteoclasts and osteoblasts) that are stimulated by tumor-secreted factors. Drugs can also inhibit tumor responses to factors enriched in the bone microenvironment, such as transforming growth factor-β. Animal models show that these approaches, especially combination treatments, can reduce tumor burden. The results suggest a novel paradigm in which tumor growth can be effectively inhibited by drugs that target cells in the bone microenvironment and not the tumor cells themselves.

Original languageEnglish (US)
Pages (from-to)1333-1342
Number of pages10
JournalJournal of Cellular Biochemistry
Volume102
Issue number6
DOIs
StatePublished - Dec 15 2007

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Keywords

  • Bisphosphonates
  • Bone metastases
  • Endothelin-1
  • Hypoxia
  • Osteoblastic metastases
  • Osteolytic metastases
  • Transforming growth factor beta
  • Wnt signaling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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