Although targeted therapy against VEGF and mTOR have revolutionized the treatment of advanced renal cell carcinoma (RCC), additional agents are required due to toxicity and resistance to currently available drugs. Some next-generation tyrosine kinase inhibitors have focused on VEGF, narrowing the spectrum of receptors which are inhibited and enhancing binding affinity. However, targeting novel receptors with tyrosine kinase inhibition of additional receptor targets has also emerged as an important future therapeutic strategy for RCC, both clear cell and variant histology. New pathways being targeted include FGF, angiopoietin and MET. In this review, we highlight five novel tyrosine kinase inhibitors in development for RCC: tivozanib; dovitinib; regorafenib; cabozantinib; and tivantinib.
Trial registration: ClinicalTrials.gov NCT01472081.