10780432ccr171606-sup-184372_3_supp_4332393_p08pgd.xlsx (40.81 kB)
Supplemental Table 1 from Venetoclax Is Effective in Small-Cell Lung Cancers with High BCL-2 Expression
dataset
posted on 2023-03-31, 20:07 authored by Timothy L. Lochmann, Konstantinos V. Floros, Mitra Naseri, Krista M. Powell, Wade Cook, Ryan J. March, Giovanna T. Stein, Patricia Greninger, Yuki Kato Maves, Laura R. Saunders, Scott J. Dylla, Carlotta Costa, Sosipatros A. Boikos, Joel D. Leverson, Andrew J. Souers, Geoffrey W. Krystal, Hisashi Harada, Cyril H. Benes, Anthony C. FaberSupplemental Table 1 shows venetoclax screen data (AUC and IC50) across 791 solid tumor cell lines.
Funding
Wellcome Trust
NIH
NCI
Massey Cancer Center
National Cancer Institute
History
ARTICLE ABSTRACT
Purpose: Small-cell lung cancer (SCLC) is an often-fatal neuroendocrine carcinoma usually presenting as extensive disease, carrying a 3% 5-year survival. Despite notable advances in SCLC genomics, new therapies remain elusive, largely due to a lack of druggable targets.Experimental Design: We used a high-throughput drug screen to identify a venetoclax-sensitive SCLC subpopulation and validated the findings with multiple patient-derived xenografts of SCLC.Results: Our drug screen consisting of a very large collection of cell lines demonstrated that venetoclax, an FDA-approved BCL-2 inhibitor, was found to be active in a substantial fraction of SCLC cell lines. Venetoclax induced BIM-dependent apoptosis in vitro and blocked tumor growth and induced tumor regressions in mice bearing high BCL-2–expressing SCLC tumors in vivo. BCL-2 expression was a predictive biomarker for sensitivity in SCLC cell lines and was highly expressed in a subset of SCLC cell lines and tumors, suggesting that a substantial fraction of patients with SCLC could benefit from venetoclax. Mechanistically, we uncover a novel role for gene methylation that helped discriminate high BCL-2–expressing SCLCs.Conclusions: Altogether, our findings identify venetoclax as a promising new therapy for high BCL-2–expressing SCLCs. Clin Cancer Res; 24(2); 360–9. ©2017 AACR.Usage metrics
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