Toward chemotherapy for Tsc2-mutant renal tumor.

Recent genetic studies of Drosophila melanogaster and subsequent biochemical analysis in mammalian cells revealed that products of tuberous sclerosis genes, TSC1 and TSC2, regulate insulin signaling via suppression of p70 ribosomal S6 subunit-kinase (S6K) activity. In this study, using transplantation in the nude mouse, we found that the growth of a renal tumor cell line from Tsc2 knockout mouse was suppressed by the treatment of rapamycin, an inhibitor of mTOR (mammalian target of rapamycin) which is an upstream activator of S6K. The robust in vivo effect of rapamycin suggests that it can be used for chemotherapy of tuberous sclerosis-associated hamartomas and tumors. Other yet undiscovered chemicals selectively downregulate mTOR-S6K pathway may provide new therapeutic drugs for tuberous sclerosis.