{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T20:42:14Z","timestamp":1771533734382,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tuberous sclerosis complex (TSC) is a familial tumor disorder for which there is no effective medical therapy. Disease\u2010causing mutations in the <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic> gene lead to increased mammalian target of rapamycin (mTOR) kinase activity in the conserved mTOR signaling pathway, which regulates nutrient uptake, cell growth, and protein translation. The normal function of <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic> gene products is to form a complex that reduces mTOR kinase activity. Thus, mTOR kinase inhibition may be a useful targeted therapeutic approach. Elevated interferon\u2010gamma (IFN\u2010\u03b3) expression is associated with decreased severity of kidney tumors in TSC patients and mouse models; therefore, IFN\u2010\u03b3 also has therapeutic potential. We studied cohorts of <jats:italic>Tsc2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice and a novel mouse model of <jats:italic>Tsc2\u2010<\/jats:italic>null tumors in order to evaluate the efficacy of targeted therapy for TSC. We found that treatment with either an mTOR kinase inhibitor (CCI\u2010779, a rapamycin analog) or with IFN\u2010\u03b3 reduced the severity of TSC\u2010related disease without significant toxicity. These results constitute definitive preclinical data that justify proceeding with clinical trials using these agents in selected patients with TSC and related disorders. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20118","type":"journal-article","created":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T17:49:18Z","timestamp":1101923358000},"page":"213-227","source":"Crossref","is-referenced-by-count":143,"title":["Efficacy of a rapamycin analog (CCI\u2010779) and IFN\u2010\u03b3 in tuberous sclerosis mouse 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