[Current strategies in the treatment of renal-cell cancer: targeted therapies].
Renal-cell carcinoma represents 95% of all renal tumours. The Von Hippel-Lindau (VHL) tumor-suppressor gene is mutated or silenced in most clear cell renal carcinomas. pVHL loss results in the stabilization of the heterodimeric transcription factor hypoxia-inducible factor (HIF) and enhanced transactivation of HIF target genes. HIF itself has been difficult to inhibit with drug-like molecules although a number of agents that indirectly inhibit HIF, including mTOR (mammalian target of rapamycin) inhibitors, have been identified. Moreover, a number of drugs have been developed that target HIF-responsive gene products, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), implicated in tumor angiogenesis. Many of these targeted therapies, especially sunitinib, have demonstrated significant activity in kidney cancer clinical trials and represent a substantive advance in the treatment of this disease.
Trigo
José Manuel
JM
Servicio de Oncología Médica, Hospital Universitario Virgen de la Victoria, Málaga, España. jmtrigo@seom.org
Bellmunt
Joaquim
J
D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human