American Association for Cancer Research
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Supplementary Figure 1 from Potential Advantages of CUDC-101, a Multitargeted HDAC, EGFR, and HER2 Inhibitor, in Treating Drug Resistance and Preventing Cancer Cell Migration and Invasion

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journal contribution
posted on 2023-04-03, 14:05 authored by Jing Wang, Natalie W. Pursell, Maria Elena S. Samson, Ruzanna Atoyan, Anna W. Ma, Abdelkader Selmi, Wanlu Xu, Xiong Cai, Maurizio Voi, Pierre Savagner, Cheng-Jung Lai

PDF file - 185K, Growth inhibitory IC50s of indicated compounds in parental and erlotinib-TR HCC827 cells.



CUDC-101 is a novel, small-molecule, anticancer agent targeting histone deacetylase (HDAC), EGF receptor (EGFR), and HER2. It is currently in phase I clinical development in patients with solid tumors. Previously, we reported that CUDC-101 has potent antiproliferative and proapoptotic activity in cultured tumor cells and in vivo xenograft models. We now show that cancer cells that have acquired resistance to single-target EGFR inhibitors through upregulation of AXL or loss of E-cadherin remain sensitive to CUDC-101, which inhibits MET- and AXL-mediated signaling, restores E-cadherin expression, and reduces cell migration. CUDC-101 also efficiently inhibited the proliferation of MET-overexpressing non–small cell lung cancer and gastric cancer cell lines and inhibited the migration and invasion of invasive tumor cells. Taken together, these results suggest that coupling HDAC and HER2 inhibitory activities to an EGFR inhibitor may potentially be effective in overcoming drug resistance and preventing cancer cell migration. Mol Cancer Ther; 12(6); 925–36. ©2013 AACR.

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