Renal Cell Carcinoma and Targeted Therapy

Renal cell carcinoma (RCC) is generally resistant to cytotoxic chemotherapy. Clear-cell RCC (ccRCC) is the most common histology accounting for 80-90% of tumors. This chapter explores the molecular pathogenesis of RCC, and the targeted therapies that have recently been developed. The genetics of VHL disease follow the "two hit" model of tumor suppressor gene function first proposed by Knudson. Next-generation sequencing has been used to evaluate tumor heterogeneity in RCC. The chapter talks about the important signaling pathways in RCC, including the mammalian target of the rapamycin (mTOR) pathway. Renal carcinoma is a vascular tumor and VEGF has been detected in high levels in the serum of patients with RCC. With elucidation of key molecular mechanisms of disease, vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptors (VEGFR) and target of the mTOR emerged as promising targets which have now been validated in large clinical trials.