The prospect of precision therapy for renal cell carcinoma

• The therapeutic landscape of renal cell carcinoma (RCC) has greatly expanded in the last decade.
• Clinicians are used to classify RCC based on tumor histology, distinguishing the most frequent clear cell RCC type from the other RCC subtypes, which are simplistically grouped as non-clear cell RCC.
• To date, the only validated systems for prognostically stratifying patients with metastatic renal cell carcinoma rely on the evaluation of clinical factors, since no molecular biomarkers with a prognostic or predictive value have been identified so far.
• A Efforts are directed at delineating signaling pathways underlying clear cell and non-clear cell RCC carcinogenesis, possibly identifying driven-mutations as potential targets for therapy.
• Novel molecular targets for therapy (such as MET, FGFR, PD-1/PD-L1) are under investigation.

The therapeutic landscape of renal cell carcinoma (RCC) has greatly expanded in the last decade. From being a malignancy orphan of effective therapies, kidney cancer has become today a tumor with several treatment options. Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3 K-Akt-mTOR pathways).In this complex scenario it is important to find prognostic and predictive factors that can help in decision making in the treatment of mRCC.