TY - JOUR
T1 - All bone metastases are not created equal
T2 - Revisiting treatment resistance in renal cell carcinoma
AU - Brozovich, Ava
AU - Garmezy, Benjamin
AU - Pan, Tianhong
AU - Wang, Liyun
AU - Farach-Carson, Mary C.
AU - Satcher, Robert L.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/12
Y1 - 2021/12
N2 - Renal cell carcinoma (RCC) is the most common malignancy of the kidney, representing 80–90% of renal neoplasms, and is associated with a five-year overall survival rate of approximately 74%. The second most common site of metastasis is bone. As patients are living longer due to new RCC targeting agents and immunotherapy, RCC bone metastases (RCCBM) treatment failure is more prevalent. Bone metastasis formation in RCC is indicative of a more aggressive disease and worse prognosis. Osteolysis is a prominent feature and causes SRE, including pathologic fractures. Bone metastasis from other tumors such as lung, breast, and prostate cancer, are more effectively treated with bisphosphonates and denosumab, thereby decreasing the need for palliative surgical intervention. Resistance to these antiresportives in RCCBM reflects unique cellular and molecular mechanisms in the bone microenvironment that promote progression via inhibition of the anabolic reparative response. Identification of critical mechanisms underlying RCCBM induced anabolic impairment could provide needed insight into how to improve treatment outcomes for patients with RCCBM, with the goals of minimizing progression that necessitates palliative surgery and improving survival.
AB - Renal cell carcinoma (RCC) is the most common malignancy of the kidney, representing 80–90% of renal neoplasms, and is associated with a five-year overall survival rate of approximately 74%. The second most common site of metastasis is bone. As patients are living longer due to new RCC targeting agents and immunotherapy, RCC bone metastases (RCCBM) treatment failure is more prevalent. Bone metastasis formation in RCC is indicative of a more aggressive disease and worse prognosis. Osteolysis is a prominent feature and causes SRE, including pathologic fractures. Bone metastasis from other tumors such as lung, breast, and prostate cancer, are more effectively treated with bisphosphonates and denosumab, thereby decreasing the need for palliative surgical intervention. Resistance to these antiresportives in RCCBM reflects unique cellular and molecular mechanisms in the bone microenvironment that promote progression via inhibition of the anabolic reparative response. Identification of critical mechanisms underlying RCCBM induced anabolic impairment could provide needed insight into how to improve treatment outcomes for patients with RCCBM, with the goals of minimizing progression that necessitates palliative surgery and improving survival.
KW - Anabolic failure
KW - Bisphosphonate
KW - Bone
KW - Denosumab
KW - Metastasis
KW - Renal cell carcinoma
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U2 - 10.1016/j.jbo.2021.100399
DO - 10.1016/j.jbo.2021.100399
M3 - Review article
C2 - 34745857
AN - SCOPUS:85118753974
SN - 2212-1374
VL - 31
JO - Journal of Bone Oncology
JF - Journal of Bone Oncology
M1 - 100399
ER -