Renal cell carcinoma bone metastasis--elucidating the molecular targets

The development of bone metastasis from renal cell carcinoma (RCC) signals a transition to a terminal state for the patient with previously isolated disease. These patients may suffer the morbidity of severe, persistent pain, pathologic fractures, and spinal compression from vertebral metastasis before they succumb to their cancer. Although recent advancements have been made in the understanding of breast and prostate bone metastasis, there has been less knowledge in the area of metastatic RCC to the skeleton. This particular cancer in bone remains relatively resistant to standard forms of treatment such as radiation and chemotherapy. A better understanding of the biology of RCC bone metastasis is critically needed in order to improve treatment. Bone-derived cell lines and an experimental animal model have been developed in order to explore the relevant mechanisms of how RCC cells survive within and destroy the bone. This review will focus on the growth factor signaling pathways most important for the RCC-stimulated osteoclast-mediated bone destruction, namely the epidermal growth factor receptor (EGF-R) and transforming growth factor-beta receptor (TGF-betaR) pathways. By inhibiting these receptors, growth of RCC within the bone is decreased which, directly or indirectly, decreases bone destruction.