Papillary renal cell carcinoma: current progress and future directions.

Papillary renal cell carcinoma (pRCC) represents the second most common histologic variant of kidney cancer. It exhibits a different molecular signature than clear-cell carcinoma and is typically not associated with mutations in the VHL (von Hippel-Lindau) tumor suppressor gene. pRCC is less responsive to modern drugs introduced in the management of kidney cancer in the past decade. In this article, the heredity and biology of 2 main variants of pRCC are outlined. New targets that are being explored in the treatment of this disease are discussed, with particular emphasis on inhibition of mesenchymal epithelial transition (MET) and epidermal growth factor receptor (EGFR) pathways. We discuss preclinical data providing rationale for the combination of MET and EGFR inhibitors and review recently completed and ongoing clinical trials that attempt to expand our therapeutic options for this important subset of kidney cancer.