Renal cell carcinoma: how to hit the targets?

Renal cell carcinoma (RCC) is a widespread oncourological disease with a tendency towards a slow increase of incidence. In the recent decade, there has been development of numerous effective drugs targeted at different molecules that play a dominant role in RCC carcinogenesis. Understanding of RCC carcinogenesis confirms the key role of angiogenesis in maintaining the viability of renal tumours and their metastases.

We aimed to systemize numerous medicines, used to inhibit the angiogenesis in patients with advanced RCC according to their targets, and to analyze their efficacy.

There are roughly four main mechanisms of action of the targeted drugs:Blockade of circulating extracellular VEGF molecules.The selective blockade of tyrosine kinase receptors' domains.The simultaneous blockage of the tyrosine kinase receptors' domains and intracellular tyrosine kinases.The blockade of mammalian target of rapamycin (mTOR) which is responsible for support of vital functions of cancer cells. In addition to FDA officially approved drugs, numerous experimental agents have been synthesized, which are currently on initial stages of clinical studies in RCC treatment.

The results of the currently used targeted drugs demonstrate perspectives of metastatic RCC conservative treatment, that are able to prolong cancer-specific survival in previously doomed patients for up to 29 months. The development of schedules for sequential treatment or combination targeted therapy remains a current challenge. The quality of life is an important factor that influences remedy choice. The advantages and disadvantages of neoadjuvant and adjuvant targeted therapy are currently being intensively discussed.