title: 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.
authors.affiliation: Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, CNIO, Melchor Fernández Almagro 3, 28029 Madrid, Spain. crodriguez@cnio.es
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez-Antona
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Donas
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics; D054316:Biomarkers, Pharmacological; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007680:Kidney Neoplasms / Q000178:diet therapy / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D054316:Biomarkers, Pharmacological; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases