Papillary renal cell carcinoma: A review of the current therapeutic landscape

• MET mutations is associated to hereditary Papillary Renal Cancer Type 1 Syndrome, but are uncommon in sporadic forms.
• VEGF/mTOR inhibitors demonstrated a marginal benefit in pRCC and the prognosis of these patients remains poor.
• MET inhibitors demonstrated encouraging activity in preclinical and clinical study, especially in patients harboring MET germline mutation.
• Targeted immunotherapy produced objective responses and represents a new therapeutic strategy.

Renal cell carcinoma (RCC) is the most common cancer of the kidney and accounts for 2–3% of all adult malignancies. Clear cell carcinoma represents the most common histologic subtype, while papillary Renal Cell Carcinoma (pRCC) accounts for 10–20% of all renal cell cancers. While the inactivation of VHL gene can be found in the majority of clear cell carcinomas, different molecular mechanisms are involved into pRCC biology. Mutations in the MET oncogene are an essential step into the pathogenesis of hereditary pRCC forms, but they can be found only in a small rate of sporadic cases. Several agents, including anti-VEGF drugs and mTOR inhibitors, are possible options in the treatment of advanced and metastatic pRCC, following the demonstration of efficacy obtained in clinical trials including all RCC histologic subtypes. However, data specifically obtained in the subgroup of patients affected by pRCC are limited and not conclusive. Several ongoing trials are evaluating the efficacy of targeted therapy in papillary form. However, more rationale approaches based on molecular studies would help improving the outcome of these patients. Among others, MET inhibitors and targeted immunotherapy are promising new strategies for hereditary and sporadic disease. This review summarizes current knowledge on pRCC tumorigenesis and discusses recent and ongoing clinical trials with new therapeutic agents.