On completion of the chapter, the reader will be able to:
Review the epidemiology, tumor histology, and molecular pathogenesis of renal cell carcinoma (RCC).
Describe the pathophysiology of RCC with a focus on the roles of von Hippel-Lindau (VHL) and hypoxia inducible factor (HIF).
Compare and contrast historical treatments for RCC with newer targeted drug therapy in terms of mechanism of action, methods of administration, adverse effects, and efficacy.
Describe the mechanistic approaches by which targeted small molecule inhibitors interfere with the pathophysiology of RCC.
Renal cell carcinoma (RCC) is a less common malignancy that, until recently, had few treatment options that were poorly tolerated and resulted in few positive outcomes for patients. However, treatment for the disease has been revolutionized by an increased understanding of the pathophysiology of RCC. Clear cell is the predominant subtype of RCC and is the result of inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene on chromosome 3p25, which leads to increased production of growth factors such as vascular endothelial growth factor (VEGF), transforming growth factor (TGF), platelet-derived growth factor (PDGF), and others responsible for angiogenesis and cell growth.1 Before 2005, the primary therapy option for patients with advanced RCC after nephrectomy was immunotherapy with few responses and high toxicity. However, seven new drugs have been approved as first- or second-line therapy for RCC: sorafenib, sunitinib, temsirolimus, bevacizumab (in combination with interferon-α [IFN-α]), everolimus, pazopanib, and axitinib.2–7 Each drug is an ...