Cambridge Journals Online

Review Article

Molecular mechanisms and treatment of bone metastasis

Gregory A. Clinesa1 and Theresa A. Guisea1 c1 a1 Division of Endocrinology and Metabolism, The University of Virginia, Charlottesville, VA 22908-1420, USA.

Article author query clines ga   guise ta

Abstract

The metastasis of cancer cells to bone alters bone architecture and mineral homeostasis. As described by the ‘seed and soil’ hypothesis, bone represents a fertile ground for cancer cells to flourish. A ‘vicious cycle’ of reciprocal bone–cancer cellular signals occurs with osteolytic (bone-resorbing) metastases, and a similar mechanism likely modulates osteoblastic (bone-forming) metastatic lesions as well. The development of targeted therapies either to block initial cancer cell chemotaxis, invasion and adhesion or to break the ‘vicious cycle’ is dependent on a more complete understanding of bone metastases. Although bisphosphonates delay progression of skeletal metastases, it is clear that more-effective therapies are needed. Cancer-associated bone morbidity remains a major public health problem, and to improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review details scientific advances in this area.

Correspondence:

^c1 Corresponding author: Theresa A. Guise, Division of Endocrinology and Metabolism, The University of Virginia, PO Box 801419, Charlottesville, VA 22908-1419, USA. Tel: +1 434 243 0305; Fax: +1 434 982 3314; E-mail: tag4n@virginia.edu