Disease models

Mice with vHL, p53 and RB1 knocked out could be used to help screen therapies for clear cell renal cell carcinoma (ccRCC). In mice, renal epithelial cell-specific knockout of all three genes generated kidney tumors in 31 of 38 mice (82%), and the 31 mice recapitulated the clear cell and eosinophilic tumor cell morphologies, tumor necrosis, sinusoidal vascular networks in tumors and tumor gene expression profiles observed in patients. In four of the 31 mice, the receptor tyrosine kinase (RTK) inhibitor Sutent sunitinib, the mTOR inhibitor Afinitor everolimus or the generic antiseptic acriflavine each had differing effects on the individual growth of individual tumors compared with the other two drugs and the other tumors. Next steps include using the model to identify mechanisms of drug susceptibility and drug resistance.

Novartis AG markets Afinitor for a variety of cancer and transplant rejection indications...