Abstract 2239: The effect combining the KIT inhibitor Imatinib with the PI3K inhibitor BKM120 or the dual PI3K/mTOR inhibitor BEZ235 on the proliferation of gastrointestinal stromal tumor cell lines
| Autor: | Paul W. Manley, Fang Li, Shumei Qiu, Linda Battalagine, John Monahan, Joseph D. Growney |
|---|---|
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Cancer Research. 72:2239-2239 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Gastrointestinal stromal tumors (GIST) are the most common type of sarcoma found in the gastrointestinal tract, with 5,000-6,000 cases per year diagnosed in the United States. Activating mutations in KIT, or occasionally in PDGFR are present in up to 90% of GISTs. The PI3K/AKT pathway has been demonstrated to be a crucial survival pathway in imatinib-resistant GISTs. In this study, we evaluated single agent activities of the KIT inhibitor imatinib, the PI3K inhibitor BKM120 and the dual PI3K/mTOR inhibitor BEZ235, as well as the synergistic activity of the combination of imatinib with BKM120 and imatinib with BEZ235 in a panel of GIST cell lines. For example, when the antiproliferative effects of imatinib and BKM120 were evaluated in combination at concentrations from 0.37 µM to 3.3 µM, growth suppression was observed in excess of the percent inhibition achieved by imatinib or BKM120 single agent treatment in the GIST882 and GIST430 cell lines. Our results suggest that combining imatinib with BKM120 or BEZ235 may provide a therapeutic strategy for imatinib-resistant GISTs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2239. doi:1538-7445.AM2012-2239 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|