Hana Garanová, Igor Andrašina, Andrea Cipková
Advances in understanding biology and genetics of renal cell carcinoma (RCC) have led to novel targeted approaches for the treatment of metastatic RCC (mRCC). Discovery of a relationship for the VHL (von Hippel-Lindau) suppressor gene, hypoxia inducible factor-1 alpha, and vascular endothelial growth factor in the pathogenesis, has identified a pathway for targeted therapy. Angiogenesis is known to play a critical role in the growth of tumours and is an important target for the development of novel anticancer therapies (VEGF, mTOR). Temsirolimus is a selective inhibitor of mTOR (mammalian target of rapamycin). Temsirolimus binds to an intracellular protein FKBP-12, and the protein/temsirolimus complex binds and inhibits the activity of mTOR that control cell division. Temsirolimus selectively impairs the translation of cell cycle regulatory proteins and has antiangiogenic effects. Temsirolimus and everolimus, rapamycin analogues have recently been tested in phase IIII trials in the first and second line treatment in patients with advanced metastatic clear cell renal cell carcinoma. Temsirolimus is indicated for the first-line treatment of patients with advanced renal cell carcinoma who have at least three of six prognostic risk factors. Everolimus is indicated for the second line treatment of patients with advanced renal cell carcinoma whose disease had progressed on treatment with VEGF receptor tyrosine kinase inhibitors.