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3 results on '"Mishaal Yazdani"'

1. Corrigendum to 'Characterizing the Therapeutic Potential of a Potent BET Degrader in Merkel Cell Carcinoma' [Neoplasia, Volume 21, Issue 3 (2019) 322–330]

Author

Jae Eun Choi, Monique E. Verhaegen, Sahr Yazdani, Rohit Malik, Paul W. Harms, Doris Mangelberger, Jean Tien, Xuhong Cao, Yuping Wang, Marcin Cieślik, Jonathan Gurkan, Mishaal Yazdani, Xiaojun Jing, Kristin Juckette, Fengyun Su, Rui Wang, Bing Zhou, Ingrid J. Apel, Shaomeng Wang, Andrzej A. Dlugosz, and Arul M. Chinnaiyan

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2024
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2. Characterizing the Therapeutic Potential of a Potent BET Degrader in Merkel Cell Carcinoma

Author

Jae Eun Choi, Monique E. Verhaegen, Sahr Yazdani, Rohit Malik, Paul W. Harms, Doris Mangelberger, Jean Tien, Xuhong Cao, Yuping Wang, Marcin Cieślik, Jonathan Gurkan, Mishaal Yazdani, Xiaojun Jing, Kristin Juckette, Fengyun Su, Rui Wang, Bing Zhou, Ingrid J. Apel, Shaomeng Wang, Andrzej A. Dlugosz, and Arul M. Chinnaiyan

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

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.

Published
2019
Full Text
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3. Characterizing the Therapeutic Potential of a Potent BET Degrader in Merkel Cell Carcinoma

Author

Jonathan Gurkan, Fengyun Su, Kristin M. Juckette, Rohit Malik, Marcin Cieślik, Andrzej A. Dlugosz, Rui Wang, Xuhong Cao, Monique Verhaegen, Xiaojun Jing, Bing Zhou, Sahr Yazdani, Mishaal Yazdani, Jean Tien, Arul M. Chinnaiyan, Jae Eun Choi, Yuping Wang, Paul W. Harms, Ingrid J. Apel, Doris Mangelberger, and Shaomeng Wang

Subjects
0301 basic medicine, Cancer Research, Original article, BET, bromodomain and extra terminal domain, Skin Neoplasms, MCPyV, Merkel cell polyomavirus, Merkel cell polyomavirus, chemical and pharmacologic phenomena, lcsh:RC254-282, BET inhibitor, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, medicine, Humans, Hox gene, Antigens, Viral, Tumor, Gene, Polyomavirus Infections, biology, Dose-Response Relationship, Drug, Merkel cell carcinoma, Chemistry, Gene Expression Profiling, Cell Cycle, Genes, Homeobox, food and beverages, Proteins, hemic and immune systems, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, biology.organism_classification, Cell Cycle Gene, Small molecule, 3. Good health, Carcinoma, Merkel Cell, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Cell culture, 030220 oncology & carcinogenesis, Proteolysis, Cancer research, Acetanilides, Transcriptome, Heterocyclic Compounds, 3-Ring
Abstract

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.

Published
2018

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