Angiogenesis inhibition in renal cell carcinoma (rcc) treatment: mechanisms, especialities and perspectives

Renal cell carcinoma is a widespread oncourologic pathology with a tendention to increasing of morbidity. Surgery is a general method of its treatment. During last years approaches to medical treatment RCC, especially metastatic forms, have changed in principle. It has been proved the major role of von-Hippel Lindau gene mutations and angiogenesis in RCC development. After perfect understanding of especialities of angiogenesis, many modern antitumoral drugs were synthesed by leading pharmaceutical companies. The mechanism of these drugs antitumor activity is based on their ability to inhibit processes of angiogenesis, cell proliferation or both. Therapy, using such kind of anticancer drugs was named targeted therapy(TT). It is possible to classify targeted drugs depending on their targets cell-localisation. The first group - vasсular endothelial growth factor (VEGF) inhibitors; the second - selective inhibitors of extracellular domains of transmembranous tyrosinkinase receptors; the third - multitargeted tyrosinkinase inhibitors; the fourth - mammalian target of rapamycin (mTOR) inhibitors. Median of overall survival (OS), using TT, sometimes mounts to 26- 29 monthes. All of targeted drugs have their own advantages (significant prolonging OS, improvement quality of life) and disadvantages (partial response, side-effects). After 10-12 monthes using TT, treatment resistance and tumor regrowth are observed. It needs to employ sequential or combined treatment. New targeted drugs and efficacy of combination TT with surgery are investigating intensively now.