{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lopez A"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS","Pershing Square Sohn Cancer Research Alliance, Irma T. Hirschl Trust","NIGMS NIH HHS","New York State Stem Cell Science"],"pagination":["1199"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8901805"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Deregulation of the BCL-2 family interaction network ensures cancer resistance to apoptosis and is a major challenge to current treatments. Cancer cells commonly evade apoptosis through upregulation of the BCL-2 anti-apoptotic proteins; however, more resistant cancers also downregulate or inactivate pro-apoptotic proteins to suppress apoptosis. Here, we find that apoptosis resistance in a diverse panel of solid and hematological malignancies is mediated by both overexpression of BCL-XL and an unprimed apoptotic state, limiting direct and indirect activation mechanisms of pro-apoptotic BAX. Both survival mechanisms can be overcome by the combination of an orally bioavailable BAX activator, BTSA1.2 with Navitoclax. The combination demonstrates synergistic efficacy in apoptosis-resistant canc"],"journal":["Nature communications"],"pubmed_title":["Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer."],"pmcid":["PMC8901805"],"funding_grant_id":["R01 CA178394","F31CA236434","1S10OD01630","P30 CA008748","F31 CA236434","2R01CA178394","DP2 CA174499","T32 GM007491","P30 CA013330","C029154","P50 CA140146","R01 CA228216","U01 CA252048"],"pubmed_authors":["Narayanagari SR","Reyna DE","Chi P","Kopp F","Nordstrom LU","Gavathiotis E","Gitego N","Vilar E","Zhou H","Lopez A","Tsirigos A","Miranda-Roman MA"],"additional_accession":[]},"is_claimable":false,"name":"Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer.","description":"Deregulation of the BCL-2 family interaction network ensures cancer resistance to apoptosis and is a major challenge to current treatments. Cancer cells commonly evade apoptosis through upregulation of the BCL-2 anti-apoptotic proteins; however, more resistant cancers also downregulate or inactivate pro-apoptotic proteins to suppress apoptosis. Here, we find that apoptosis resistance in a diverse panel of solid and hematological malignancies is mediated by both overexpression of BCL-XL and an unprimed apoptotic state, limiting direct and indirect activation mechanisms of pro-apoptotic BAX. Both survival mechanisms can be overcome by the combination of an orally bioavailable BAX activator, BTSA1.2 with Navitoclax. The combination demonstrates synergistic efficacy in apoptosis-resistant canc","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-31T04:03:32.472Z","creation":"2025-02-19T01:53:13.009Z"},"accession":"S-EPMC8901805","cross_references":{"pubmed":["35256598"],"doi":["10.1038/s41467-022-28741-7"]}}