Cooperative benefit for the combination of rapamycin and imatinib in tuberous sclerosis complex neoplasia
Curatolo, Adam S
Bonner, Michael Y.
Arbiser, Jack L
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CitationGovindarajan, Baskaran, Laura Willoughby, Hamid Band, Adam S Curatolo, Emir Veledar, Suephy Chen, Michael Y Bonner, Martin-Garrido Abel, Marsha A Moses, and Jack L Arbiser. 2012. Cooperative benefit for the combination of rapamycin and imatinib in tuberous sclerosis complex neoplasia. Vascular Cell 4:11.
AbstractTuberous sclerosis (TS) is a common autosomal-dominant disorder characterized by tumors of the skin, lung, brain, and kidneys. Monotherapy with rapamycin however resulted in partial regression of tumors, implying the involvement of additional pathways. We have previously implicated platelet-derived growth factor-BB in TS-related tumorigenesis, thus providing a rationale for a combination of mTOR/PDGF blockade using rapamycin and imatinib. Here, we test this combination using a well-established preclinical model of cutaneous tumorigenesis in TS, tsc2ang1 cells derived from a skin tumor from a mouse heterozygous for tsc2. Treatment of tsc2ang1 cells with a combination of rapamycin and imatinib led to an inhibition of proliferation compared with either vehicle treatment or treatment with rapamycin or imatinib monotherapy. Combination therapy also led to a decrease in Akt activation. Potent in vivo activity in animal experiments by combination therapy was noted, without toxicity to the animals. Our findings provide a rationale for the combined use of rapamycin and imatinib, both FDA approved drugs, for the treatment of TS.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10522858
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