Breast cancer bone metastasis and current small therapeutics

Muzaffer Cicek, Merry Jo Oursler

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Patients with advanced breast cancer frequently develop metastasis to bone. Bone metastasis results in intractable pain and a high risk of fractures due to tumor-driven bone loss (osteolysis), which is caused by increased osteoclast activity. Osteolysis releases bone-bound growth factors including transforming growth factor beta (TGF-β). The widely accepted model of osteolytic bone metastasis in breast cancer is based on the hypothesis that the TGF-β released during osteolytic lesion development stimulates tumor cell parathyroid hormone related protein (PTHrP), causing stromal cells to secrete receptor activator of NFκB ligand (RANKL), thus increasing osteoclast differentiation. Elevated osteoclast numbers results in increased bone resorption, leading to more TGF-β being released from bone. This interaction between tumor cells and the bone microenvironment results in a vicious cycle of bone destruction and tumor growth. Bisphosphonates are commonly prescribed small molecule therapeutics that target tumor-driven osteoclastic activity in osteolytic breast cancers. In addition to bisphosphonate therapies, steroidal and non-steroidal antiestrogen and adjuvant therapies with aromatase inhibitors are additional small molecule therapies that may add to the arsenal for treatment of osteolytic breast cancer. This review focuses on a brief discussion of tumor-driven osteolysis and the effects of small molecule therapies in reducing osteolytic tumor progression.

Original languageEnglish (US)
Pages (from-to)635-644
Number of pages10
JournalCancer and Metastasis Reviews
Volume25
Issue number4
DOIs
StatePublished - Dec 2006

Fingerprint

Bone Neoplasms
Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
Osteolysis
Osteoclasts
Neoplasms
Transforming Growth Factor beta
Diphosphonates
Therapeutics
Cellular Microenvironment
Parathyroid Hormone-Related Protein
Intractable Pain
Aromatase Inhibitors
Estrogen Receptor Modulators
Bone Development
Bone Resorption
Stromal Cells
Intercellular Signaling Peptides and Proteins
Ligands

Keywords

  • Anti-estrogen
  • Aromatase inhibitor
  • Bisphosphonate
  • Bone metastasis
  • Osteoclast
  • TGF-beta

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Breast cancer bone metastasis and current small therapeutics. / Cicek, Muzaffer; Oursler, Merry Jo.

In: Cancer and Metastasis Reviews, Vol. 25, No. 4, 12.2006, p. 635-644.

Research output: Contribution to journalArticle

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