Foretinib (XL880): c-MET inhibitor with activity in papillary renal cell cancer.

Papillary renal cell cancer (RCC) constitutes approximately 10 % of renal cancers and is the commonest form after clear cell RCC, which accounts for approximately 75 % of cases. Until recently, most clinical trials in RCC were open to patients of all histologic types. Very recent clinical trials have been performed predominately in patients with clear cell RCC and relatively few trials have been done for patients with papillary RCC. The clinical characteristics of papillary RCC are less well appreciated because of both its relative rarity in the general oncology population and the lack of related clinical studies. This article reviews papillary RCC as a clinical entity separate from clear cell RCC. The MET signaling pathway, its association with increased invasion and progression of human cancer, and its dysregulation in papillary RCC is discussed. Lastly, foretinib, a multitargeted receptor tyrosine kinase inhibitor of several receptors, including MET and vascular endothelial growth factor receptor 2, is described in preclinical and phase I studies as well as in a phase II study in papillary RCC patients.