Molecularly targeted therapy in renal cell carcinoma.
Recent developments in the molecular biology of renal cell carcinoma have identified multiple pathways associated with the development of this cancer. Multiple strategies have been investigated targeting these pathways, with significant clinical benefits shown in early studies. This review aims to overview the findings of recent clinical trials and clarify the development of these compounds for use in renal cell carcinoma. The authors also aim to clarify the molecular pathways implicated in renal cell carcinoma and the clinical results in metastatic renal cell carcinoma with agents targeting these pathways. The relevant literature was reviewed concerning pathways implicated in the pathophysiology of renal cell carcinoma including pathways activated secondary to von Hippel-Lindau gene inactivation and PI-3 kinase/Akt/mammalian target of rapamycin pathway activation. Therapeutic targeting based upon underlying molecular biology in renal cell carcinoma has strong rationale. Substantial clinical activity has been reported with various agents targeting these pathways, most notably with vascular endothelial growth factor-targeted therapy. However, investigation is needed to optimally utilize these agents at the appropriate stage of disease and in the best combinations for maximal clinical benefit.
Rathmell
W Kimryn
WK
Lineberger Comprehensive Cancer Center, University of North Carolina, Campus Box 7295, Chapel Hill, NC 27599-7295, USA. rathmell@med.unc.edu
Wright
Tricia M
TM
Rini
Brian I
BI
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011494:Protein Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000502:physiology
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C497446:VHL protein, human