Abstract
Clear cell renal cell carcinoma (ccRCC) is the seventh most frequently diagnosed tumor in adults in Europe and represents approximately 2.5% of cancer deaths. The molecular biology underlying renal cell carcinoma (RCC) development and progression has been a key milestone in the management of this type of tumor. The discovery of Von Hippel Lindau (VHL) gene alterations that arouse in 50% of ccRCC patients, leads the identification of an intracellular accumulation of HIF and, consequently an increase of VEGFR expression. This change in cell biology represents a new paradigm in the treatment of metastatic renal cancer by targeting angiogenesis. Currently, there are multiple therapeutic drugs available for advanced disease, including therapies against VEGFR with successful results in patients´ survival. Other tyrosine kinases’ pathways, including PDGFR, Axl or MET have emerged as key signaling pathways involved in RCC biology. Indeed, promising new drugs targeting those tyrosine kinases have exhibited outstanding efficacy. In this review we aim to present an overview of the central role of these tyrosine kinases’ activities in relevant biological processes for kidney cancer and their usefulness in RCC targeted therapy development. In the immunotherapy era, angiogenesis is still an “old guy” that the medical community is trying to fight using “new bullets”.
Highlights
Kidney cancer represents the third tumor of the urinary tract most frequently diagnosed in adults
The results showed an overall response rate (ORR) of 30% versus 3% for pazopanib compared with the placebo, respectively
After a median follow up of 25 months updated results were presented: HR for progression-free survival (PFS) was 0.56 and the ORR was 20% for cabozantinib versus 9% for sunitinib by blinded independent-central review (BICR) and 33% for cabozantinib versus 12% for sunitinib by investigator assessment
Summary
Kidney cancer represents the third tumor of the urinary tract most frequently diagnosed in adults. In Europe, the incidence of clear cell renal cell carcinoma (ccRCC) accounts for 84,000 new cases per year with a mortality rate of about 35,000 patients in 2012 [1]. The clear cell subtype is the most common one representing approximately 85% to 90% of all renal cancer diagnosis [2]. In countries from Northern and Eastern Europe, Australia and US, the mortality tends to stabilize or even decline [3]. The incidence of kidney cancer is greater in men than women (ratio of 2:1) [4] and it is usually diagnosed around the sixth decade of life (median age around 67 years)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
