%0 Journal Article
%T Characterizing the Therapeutic Potential of a Potent BET Degrader in Merkel Cell Carcinoma
%A Andrzej A. Dlugosz
%A Arul M. Chinnaiyan
%A Bing Zhou
%A Doris Mangelberger
%A Fengyun Su
%A Ingrid J. Apel
%A Jae Eun Choi
%A Jean Tien
%A Jonathan Gurkan
%A Kristin Juckette
%A Marcin Cie£¿lik
%A Mishaal Yazdani
%A Monique E. Verhaegen
%A Paul W. Harms
%A Rohit Malik
%A Rui Wang
%A Sahr Yazdani
%A Shaomeng Wang
%A Xiaojun Jing
%A Xuhong Cao
%A Yuping Wang
%J Archive of "Neoplasia (New York, N.Y.)".
%D 2019
%R 10.1016/j.neo.2019.01.003
%X Studies on the efficacy of small molecule inhibitors in Merkel cell carcinoma (MCC) have been limited and largely inconclusive. In this study, we investigated the therapeutic potential of a potent BET degrader, BETd-246, in the treatment of MCC. We found that MCC cell lines were significantly more sensitive to BETd-246 than to BET inhibitor treatment. Therapeutic targeting of BET proteins resulted in a loss of ¡°MCC signature¡± genes but not MYC expression as previously described irrespective of Merkel cell polyomavirus (MCPyV) status. In MCPyV+ MCC cells, BETd-246 alone suppressed downstream targets in the MCPyV-LT Ag axis. We also found enrichment of HOX and cell cycle genes in MCPyV£¿ MCC cell lines that were intrinsically resistant to BETd-246. Our findings uncover a requirement for BET proteins in maintaining MCC lineage identity and point to the potential utility of BET degraders for treating MCC
%K MCPyV
%K Merkel cell polyomavirus
%K BET
%K bromodomain and extra terminal domain
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384317/