Advances Against Papillary RCC

Type I papillary RCC may occur in either a hereditary or a sporadic, non-hereditary form. Identification of activating mutations in the tyrosine kinase domain of the proto-oncogene MET in patients with hereditary papillary RCC and a subset of patients with sporadic papillary RCC prompted a multicenter phase II study of foretinib, a tyrosine kinase inhibitor.


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Although the overall response rate was only 13.5%, mean progression-free survival was 9.3 months, substantially higher than that typically seen in patients with this disease. Trials of other agents targeting Met in type I papillary RCC are under way.

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Metabolic factors play an important role in type II papillary RCC and may point to new therapeutic approaches. In fumarate hydratase (FH)–deficient RCC, oxidative phosphorylation is impaired and a shift to aerobic glycolysis is seen.

This form of RCC is highly dependent on glucose for proliferation. The resulting oxidative stress makes continued growth of FH-deficient RCC dependent on effective antioxidant response. Each of these metabolic steps may one day be found to be vulnerable to targeted therapies.

Reference

  1. Srinivasan R, Ricketts CJ, Sourbier C, Linehan WM. New strategies in renal cell carcinoma: targeting the genetic and metabolic basis of disease. Clin Cancer Res. 2015;21(1):10-17.