Evolution and innovations in the systemic treatment landscape of renal cell carcinoma

Treatments for metastatic renal cell carcinoma are constantly changing thanks to the increasing knowledge of the molecular biology of this tumor. In fact, understanding the underlying genetic mechanisms has led to the development of new classes of drugs, known as molecularly targeted therapies that, to date, represent the standard treatment in the first-line setting. More recently, we have witnessed the resurgence of immunotherapy, which is providing significant benefit to patients with treatment-refractory disease. The use of all of the currently available agents, in sequence, has been shown to prolong survival to beyond 20 months, and to improve the quality of life of patients. Despite the recent progress, there is still a crucial need for further advances. The discovery of biomarkers that would allow the prediction of treatment response and therefore lead to better patient selection, as well as understanding the potential mechanisms of acquired resistance that might guide the choice of the optimal sequential use of the available drugs, together still represent an open challenge for both scientists and clinicians.