Cooperative benefit for the combination of rapamycin and imatinib in tuberous sclerosis complex neoplasia

Baskaran Govindarajan, Laura Willoughby, Hamid Band, Adam S. Curatolo, Emir Veledar, Suephy Chen, Michael Y. Bonner, Martin Garrido Abel, Marsha A. Moses, Jack L. Arbiser

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Tuberous 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.

Original languageEnglish (US)
Article number11
JournalVascular Cell
Volume4
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Computer Networks and Communications
  • Cell Biology

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    Govindarajan, B., Willoughby, L., Band, H., Curatolo, A. S., Veledar, E., Chen, S., Bonner, M. Y., Abel, M. G., Moses, M. A., & Arbiser, J. L. (2012). Cooperative benefit for the combination of rapamycin and imatinib in tuberous sclerosis complex neoplasia. Vascular Cell, 4, [11]. https://doi.org/10.1186/2045-824X-4-11