Constitutional Genetic Variants as Predictors of Antiangiogenic Therapy Outcome in Renal Cell Carcinoma

Abstract

The development of specific angiogenesis inhibitors has drastically improved renal cancer treatment in recent years. Currently, four VEGF receptor inhibitors (sorafenib, sunitinib, pazopanib and axitinib), one anti-VEGF monoclonal antibody (bevacizumab) and two inhibitors of the mTOR pathway (temsirolimus and everolimus) have been approved to treat renal cell carcinoma (RCC), and several other molecules are under investigation. However, lack of response to antiangiogenic drugs and adverse drug reactions leading to treatment suspension are critical clinical problems that need to be solved. Because antiangiogenic drugs act on nonmalignant endothelial cells, the genetic background of the patient may play a crucial role determining the efficacy of these drugs. This article focuses on the identification of polymorphisms associated with antiangiogenic drugs outcome in RCC patients. It reviews and summarizes our current knowledge on this area and discusses future strategies to identify new biomarkers that could be used to personalize RCC management.

KEYWORDS::

• antiangiogenic drugs
• axitinib
• bevacizumab
• pazopanib
• polymorphisms
• renal cell carcinoma
• sunitinib

Financial & competing interests disclosure

J García-Donas has been a consultant for Pfizer, Glaxo, Novartis and Aveo, Inc., and has received funds for investigation from Pfizer and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

J García-Donas has been a consultant for Pfizer, Glaxo, Novartis and Aveo, Inc., and has received funds for investigation from Pfizer and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.