00085472can151458-sup-150379_2_supp_3249567_nyp8pb.xlsx (9.6 kB)
Cell line information from Preclinical Anticancer Efficacy of BET Bromodomain Inhibitors Is Determined by the Apoptotic Response
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posted on 2023-03-30, 23:46 authored by Andrew R. Conery, Richard C. Centore, Kerry L. Spillane, Nicole E. Follmer, Archana Bommi-Reddy, Charlie Hatton, Barbara M. Bryant, Patricia Greninger, Arnaud Amzallag, Cyril H. Benes, Jennifer A. Mertz, Robert J. SimsThis file contains the source of all cell lines used for the work described in the manuscript as well as the methods by which cell lines are authenticated at the repositories.
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ARTICLE ABSTRACT
Small-molecule inhibitors of the bromodomain and extraterminal (BET) family of proteins are being tested in clinical trials for a variety of cancers, but patient selection strategies remain limited. This challenge is partly attributed to the heterogeneous responses elicited by BET inhibition (BETi), including cellular differentiation, senescence, and death. In this study, we performed phenotypic and gene-expression analyses of treatment-naive and engineered tolerant cell lines representing human melanoma and leukemia to elucidate the dominant features defining response to BETi. We found that de novo and acquired tolerance to BETi is driven by the robustness of the apoptotic response, and that genetic or pharmacologic manipulation of the apoptotic signaling network can modify the phenotypic response to BETi. We further reveal that the expression signatures of the apoptotic genes BCL2, BCL2L1, and BAD significantly predict response to BETi. Taken together, our findings highlight the apoptotic program as a determinant of response to BETi, and provide a molecular basis for patient stratification and combination therapy development. Cancer Res; 76(6); 1313–9. ©2016 AACR.Usage metrics
Keywords
Cancer PreventionIdentification of new risk factorsCell Death And SenescenceTranscriptional control of apoptosisbcl-2 pathwaysDrug MechanismsCellular responses to anticancer drugsDrug ResistanceRegulation of gene expression in drug resistanceGenome BiologyStructural genomicsHematological CancersLeukemiasPediatric CancersSkin Cancers
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