TY - JOUR
T1 - The critical role of the bone microenvironment in cancer metastases
AU - Casimiro, Sandra
AU - Guise, Theresa A.
AU - Chirgwin, John
N1 - Funding Information:
The authors thank the members of their laboratories including Prof. Luis Costa, Lauren Kingsley Dunn and Valerie Siclari and Drs. Pierrick Fournier, Khalid Mohammad and Gregory Clines for useful discussions and Ms. Amy Thompson for editorial assistance. Sandra Casimiro is supported by grant SFRH/BPD/34801/2007 from MCTES, Portugal. Theresa Guise and John Chirgwin are supported by grants from the NIH (CA69158, CA40035, DK065837), Department of Defense (PC010497, PC040341, PC051194), the V Foundation, the Prostate Cancer Foundation, and the Mellon Institute, the Cancer Center and the Gerald D. Aurbach Endowment of the University of Virginia.
PY - 2009/10/30
Y1 - 2009/10/30
N2 - Bone metastatic disease is a late-stage event of many common cancers, such as those of prostate and breast. It is incurable and causes severe morbidity. Tumor and bone interact in a vicious cycle, where tumor-secreted factors stimulate bone cells, which in turn release growth factors and cytokines that act back on the tumor cells. Within the vicious cycle are many potential therapeutic targets for novel treatment of bone metastatic disease. Therapeutic strategies can be oriented to inhibit bone cells (osteoclasts and osteoblasts) or tumor responses to factors enriched in the bone microenvironment. Many publications, especially from pre-clinical animal models, show that this approach, especially combination treatments, can reduce tumor burden and tumor-derived bone lesions. This supports a novel paradigm: tumor growth can be effectively inhibited by targeting the bone and its microenvironment rather than the tumor itself alone.
AB - Bone metastatic disease is a late-stage event of many common cancers, such as those of prostate and breast. It is incurable and causes severe morbidity. Tumor and bone interact in a vicious cycle, where tumor-secreted factors stimulate bone cells, which in turn release growth factors and cytokines that act back on the tumor cells. Within the vicious cycle are many potential therapeutic targets for novel treatment of bone metastatic disease. Therapeutic strategies can be oriented to inhibit bone cells (osteoclasts and osteoblasts) or tumor responses to factors enriched in the bone microenvironment. Many publications, especially from pre-clinical animal models, show that this approach, especially combination treatments, can reduce tumor burden and tumor-derived bone lesions. This supports a novel paradigm: tumor growth can be effectively inhibited by targeting the bone and its microenvironment rather than the tumor itself alone.
KW - Bone metastases
KW - Bone microenvironment
KW - Matrix metalloproteinases
KW - Osteoblastic metastases
KW - Osteolytic metastases
KW - Transforming growth factor beta
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U2 - 10.1016/j.mce.2009.07.004
DO - 10.1016/j.mce.2009.07.004
M3 - Review article
C2 - 19616059
AN - SCOPUS:69249206543
SN - 0303-7207
VL - 310
SP - 71
EP - 81
JO - Molecular and cellular endocrinology
JF - Molecular and cellular endocrinology
IS - 1-2
ER -