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  • Review Article
  • Published:

The best of both worlds — managing the cancer, saving the bone

Nature Reviews Endocrinology volume 12, pages 29–42 (2016)Cite this article

Subjects

Key Points

  • Metastatic tumours represent the greatest threat to the survival of patients with cancer

  • The development of therapies that impede the growth and/or function of tumour cells, while sparing normal host cells, is critical to improving the care of patients with cancer

  • In the case of bone metastases, cells within the bone marrow niche mediate many of the orthopaedic consequences of tumour progression as well as resistance to the antitumour effects of existing therapies

  • Osteocytes have a key role in the activation and progression of osteolytic metastases

Abstract

In the context of breast cancer, the importance of the skeleton in the regulation of primary tumour development and as a site for subsequent metastasis is well characterized. Our understanding of the contributions made by the host bone and bone marrow cells increasingly demonstrates the extent of the interaction between tumour cells and normal host cells. As a result, the need to develop and utilize therapies that can impede the growth and/or function of tumour cells while sparing normal host bone and bone marrow cells is immense and expanding. The need for these new treatments is, however, superimposed on the orthopaedic management of patients' quality of life, where pain control and continued locomotion are paramount. Indeed, the majority of the anticancer therapies used to date often result in direct or indirect damage to bone. Thus, although the bone microenvironment regulates tumour cell growth in bone, cells within the bone marrow niche also mediate many of the orthopaedic consequences of tumour progression as well as resistance to the antitumour effects of existing therapies. In this Review, we highlight the effects of existing cancer treatments on bone and the bone marrow microenvironment as well as the mechanisms mediating these effects and the current utility of modern orthopaedic interventions.

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Figure 1: Cells in the bone and bone marrow microenvironment.
Figure 2: Presentation of lytic, blastic and mixed bone lesions.

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Acknowledgements

The authors' work on the mechanisms driving tumour progression and the development of bone metastases is supported by the NIH (grant R01 CA166060 to L.J.S.) and the Carl L. Nelson Endowed Chair in Orthopaedic Creativity (L.J.S.).

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Authors and Affiliations

  1. Department of Medicine, Division of Haematology/Oncology Winthrop P. Rockefeller Cancer Institute, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, 72205, AR, USA

    Issam Makhoul

  2. Department of Orthopaedic Surgery, Centre for Orthopaedic Research, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR, 72205, USA

    Corey O. Montgomery & Larry J. Suva

  3. Department of Physiology and Biophysics, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, 72205, AR, USA

    Dana Gaddy

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I.M., C.O.M., D.G. and L.J.S. researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Larry J. Suva.

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Makhoul, I., Montgomery, C., Gaddy, D. et al. The best of both worlds — managing the cancer, saving the bone. Nat Rev Endocrinol 12, 29–42 (2016). https://doi.org/10.1038/nrendo.2015.185

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