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Supplementary tables 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. Sims

This file contains 4 supplementary tables: Table S1 provides the expression values of the indicated genes (RMA) in BETi sensitive and insensitive cell lines; Table S2 shows the enrichment of subtypes of cell lines following selection with the indicated criteria; Table S3 shows SNP analysis of parental and BETi tolerant A375 cells; Table S4 shows SNP analysis of parental and BETi tolerant NOMO-1 cells.

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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.

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    Cancer Research

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    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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