title: BCL-2: Long and winding path from discovery to therapeutic target.
abstract: In 1988, the BCL-2 protein was found to promote cancer by limiting cell death rather than enhancing proliferation. This discovery set the wheels in motion for an almost 30 year journey involving many international research teams that has recently culminated in the approval for a drug, ABT-199/venetoclax/Venclexta that targets this protein in the treatment of cancer. This review will describe the long and winding path from the discovery of this protein and understanding the fundamental process of apoptosis that BCL-2 and its numerous homologues control, through to its exploitation as a drug target that is set to have significant benefit for cancer patients.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Schenk
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia. Electronic address: dewson@wehi.edu.au.
authors.forename: Grant
authors.initials: G
authors.lastname: Dewson
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015195:Drug Design; D055808:Drug Discovery; D019254:Genes, bcl-2; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology; D060066:Protein Interaction Maps; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C579720:venetoclax; C528561:navitoclax
keywords: ABT-199; Apoptosis; BCL-2; BH3-Mimetics; Cancer; Venetoclax