Novel Therapeutic Approaches and the Evolution of Drug Development in Advanced Kidney Cancer

Therapies currently approved in renal cell carcinoma (RCC) include tyrosine kinase inhibitors, immune checkpoint inhibitors, and inhibitors of mTOR signaling. Increased understanding of the biology of clear cell and non-clear cell RCC has led to development of agents that target hypoxia-inducible factor 2 and MET, while there is ongoing exploration of targeting immune pathways other than the programmed death ligand 1 or cytotoxic T-lymphocyte-associated protein 4 checkpoints. Drug development in RCC is moving toward the study of combination therapies and attempting to use a risk-adapted approach in treatment. While the past decade has seen the approval of several new therapies, there is an urgent need to focus drug development on novel targets and expand the therapeutic armamentarium in both clear cell and non-clear cell kidney cancer. This review provides an overview of the key targets currently undergoing clinical evaluation, as well as how drug development has evolved over the past 20 years and what the new few years may hold.