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.
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.
- 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.