Osteolytic metastasis in breast cancer: effective prevention strategies

ABSTRACT

Introduction

Breast cancer is the most common cancer in women throughout the world. Patients who are diagnosed early generally have better prognosis and survivability. Indeed, advanced stage breast cancer often develops osteolytic metastases, leading to bone destruction. Although there are select drugs available to treat bone metastatic disease, these drugs have shown limited success.

Area covered

This paper emphasizes updated mechanisms of bone remodeling and osteolytic bone metastases of breast cancer. This article also aims to explore the potential of novel natural and synthetic therapeutics in the effective prevention of breast cancer-induced osteolysis and osteolytic metastases of breast cancer.

Expert opinion

Targeting TGFβ and BMP signaling pathways, along with osteoclast activity, appears to be a promising therapeutic strategy in the prevention of breast cancer-induced osteolytic bone destruction and metastatic growth at bone metastatic niches. Pilot studies in animal models suggest various natural and synthetic compounds and monoclonal antibodies as putative therapeutics in the prevention of breast cancer stimulated osteolytic activity. However, comprehensive pre-clinical studies demonstrating the PK/PD and in-depth understanding of molecular mechanism(s) by which these potential molecules exhibit anti-tumor growth and anti-osteolytic activity are still required to develop effective therapies against breast cancer-induced osteolytic bone disease.

KEYWORDS:

• Breast cancer
• bone remodeling
• bone metastasis
• osteolysis
• osteoclast activity
• prevention strategy
• potential molecules

Article highlights

• Apart from CSF-1 and RANKL, bone resident cells share various molecules to maintain bone homeostasis by performing balanced bone remodeling.

• Targeting of TGFβ and BMP signaling in addition to osteoclast activity may hold promise in preventing bone destruction and metastatic growth of breast cancer.

• Various natural and synthetic molecules (e.g. statins, omega-3 fatty acids, vitamins, curcumin, rapamycin, quetiapine, A77636, etc.) may be potential drug candidates in preventing osteolytic breast cancer, which may overcome the limitation of denosumab and bisphosphonates.

• In-depth molecular understanding of these drug candidates and how they are involved in anti-tumor and anti-osteolytic activity may also guide suitable combination therapy for the treatment of breast cancer-induced bone metastases.

Acknowledgments

The author also wishes to thank Dr. Bridget M. Ford, Department of Biology, University of the Incarnate Word, San Antonio, Texas-78209, USA for critical reading and editing of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The author is thankful to DST-RFBR grant (INT/RUS/RFBR/P-256), India and Central University of Rajasthan, India for the financial support.