Renal cell carcinoma: molecular characterization and evolving treatment paradigms

Purpose of review: The treatment landscape of advanced renal cell carcinoma (RCC) continues to shift as both new targeted therapies and immunotherapies show efficacy in treating the disease. Contemporary insights into the molecular characterization of RCC are likely to fuel the development of additional therapies. This review summarizes recent advancements in the biologic characterization of RCC and discusses newly approved therapies and ongoing studies in the treatment of advanced RCC. Recent findings: The Cancer Genome Atlas has now completed comprehensive molecular characterization of clear cell, papillary, and chromophobe RCC, providing insights into the biology of these entities. Two new 'targeted' therapies, cabozantinib and lenvatinib, as well as a novel immune checkpoint inhibitor, the programed death 1 inhibitor nivolumab, have recently been approved for the treatment of metastatic RCC. Although some of these newer therapies are associated with prolongation of survival, there are few long-term responders and the quest for more durable treatment strategies continues. Summary: The addition of several new agents effective in metastatic RCC has resulted in improvements in overall survival; however, there are few avenues to durable responses or cure. Ongoing studies as well advances in our understanding of the molecular alterations underlying distinct forms of RCC promise further therapeutic advances and have the potential to alter the current treatment paradigm.

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