Antiangiogenic tyrosine kinase inhibitors have differential efficacy in clear cell renal cell carcinoma in bone.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney neoplasm; bone metastasis (BM) develops in 35-40% of metastatic patients and results in substantial morbidity and mortality, as well as medical costs. A key feature of ccRCC is the loss of function of the von Hippel-Lindau (VHL) protein, which enhances angiogenesis via vascular endothelial growth factor release. Consequently, anti-angiogenic tyrosine kinase inhibitors (TKIs) emerged as a treatment for ccRCC. However, limited data about their efficacy in BM is available, and no systematic comparisons have been performed. We developed mouse models of bone and lung ccRCC tumors and compared their anti-cancer efficacy, impact on mouse survival, and mechanisms of action, including effects on tumor cells and both immune and non-immune (blood vessels, osteoclasts) bone stromal components. This approach elucidates the efficacy of TKIs in ccRCC bone tumors to support rational interrogation and development of therapies.