Journal Article

Bone metastasis: mechanisms and therapeutic opportunities

Nicholas, Richard W., Washam, Charity, Suva, Larry J., Griffin, Robert J.

2011

Overview

The growth of disseminated tumor metastases is a major cause of mortality in patients with cancer, and bone is a common site for metastasis. This Review summarizes the cellular and molecular components of the metastatic cascade and highlights potential new directions for future therapeutic strategies to target bone metastasis. The skeleton is one of the most common sites for metastatic cancer, and tumors arising from the breast or prostate possess an increased propensity to spread to this site. The growth of disseminated tumor cells in the skeleton requires tumor cells to inhabit the bone marrow, from which they stimulate local bone cell activity. Crosstalk between tumor cells and resident bone and bone marrow cells disrupts normal bone homeostasis, which leads to tumor growth in bone. The metastatic tumor cells have the ability to elicit responses that stimulate bone resorption, bone formation or both. The net result of these activities is profound skeletal destruction that can have dire consequences for patients. The molecular mechanisms that underlie these painful and often incurable consequences of tumor metastasis to bone are beginning to be recognized, and they represent promising new molecular targets for therapy. Key Points Bone is a common site of metastasis for many tumors, such as breast, lung and prostate cancer A continuum of bone metastasis exists that extends from primarily osteolytic lesions with limited osteoblast activity to bone metastases that are predominantly osteoblastic, with limited osteoclast activity The complex interactions between circulating tumor cells, circulating host cells, platelets and cell-derived factors are critical for tumor establishment at metastatic sites Tumor activation of bone resorption is complex and involves both receptor activator of nuclear factor κB ligand (RANKL)-dependent and RANKL-independent mechanisms Targeting bone resorption with bisphosphonates reduces osteolytic bone resorption and improves disease-free survival All steps in the metastatic process and the interaction with host cells are valid therapeutic targets for the treatment of bone metastasis and tumor progression

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/699/67/1059/602 / 692/699/67/322/803 / Bone cancer / Bone marrow / Bone Neoplasms - drug therapy / Bone Neoplasms - metabolism / Bone Neoplasms - secondary / Bone surgery / Breast cancer / Breast Neoplasms - complications / Breast Neoplasms - metabolism / Cancer therapies / Care and treatment / Development and progression / Endocrinology / Female / Health aspects / Humans / Male / Medicine / Medicine & Public Health / Metastasis / Models, Biological / Orthopedics / Prostate cancer / Prostatic Neoplasms - complications / Prostatic Neoplasms - metabolism / review-article / Risk factors / Signal Transduction / Tumors