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- W2058961982 abstract "CUDC-101 is a novel small-molecule multi-target anti-cancer agent currently in Phase Ib clinical trial, which targets histone deacetylase (HDAC), epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor2 (HER2). Previously, we reported that CUDC-101 has potent anti-proliferative and pro-apoptotic activities in cultured tumor cells and in vitro xenograft models when compared to other single-target agents. Additionally, we demonstrated that CUDC-101 reduces the levels of phosphorylated and total MET. MET amplification and secondary EGFR mutation are two validated mechanisms responsible for EGFR tyrosine kinase inhibitor (TKI) drug resistance in patients. In an effort to expand on our previous findings, we further substantiate here that cancer cells harboring MET amplification are sensitive to CUDC-101. This result, together with the finding that cancer cells containing the EGFR-T790M mutation are sensitive to CUDC-101, suggests that RTK inhibitor-resistant tumor cells are sensitive to treatment with CUDC-101. Additionally, erlotinib-resistant HCC827 cells, which lost their EGFR dependence, are still sensitive to treatment with CUDC-101. Interestingly, this drug-resistant cell line shows neither secondary EGFR mutation nor c-Met amplification, suggesting that CUDC-101 has the potential to overcome drug resistance through other mechanisms. Because c-Met plays an important role in metastasis, we further investigated the effect of CUDC-101 in regulating cell motility, and demonstrate that CUDC-101 can induce E-cadherin accumulation in MDA-MB-231 cells and inhibit EGF induced epithelial-mesenchymal transition (EMT) in in vitro cultured cell and in vivo animal models. In vitro functional study also shows that CUDC-101 reduces tumor cell migration and invasion. Together, our findings suggest that CUDC-101, an investigational anti-cancer drug, may provide great potential for simultaneously overcoming tumor growth, metastasis, and drug resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2619. doi:10.1158/1538-7445.AM2011-2619" @default.
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- W2058961982 date "2011-04-15" @default.
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- W2058961982 title "Abstract 2619: Potential advantages of CUDC-101, a multi-targeted HDAC, EGFR and HER2 inhibitor, on preventing drug resistance and tumor metastasis" @default.
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