title: BH3 profiling and a toolkit of BH3-mimetic drugs predict anti-apoptotic dependence of cancer cells.
abstract: BACKGROUND
  Anti-apoptotic BCL-2 family members antagonise apoptosis by sequestering their pro-apoptotic counterparts. The balance between the different BCL-2 family members forms the basis of BH3 profiling, a peptide-based technique used to predict chemosensitivity of cancer cells. Recent identification of cell-permeable, selective inhibitors of BCL-2, BCL-XL and MCL-1, further facilitates the determination of the BCL-2 family dependency of cancer cells.
  
  
  METHODS
  We use BH3 profiling in combination with cell death analyses using a chemical inhibitor toolkit to assess chemosensitivity of cancer cells.
  
  
  RESULTS
  Both BH3 profiling and the inhibitor toolkit effectively predict chemosensitivity of cells addicted to a single anti-apoptotic protein but a combination of both techniques is more instructive when cell survival depends on more than one anti-apoptotic protein.
  
  
  CONCLUSIONS
  The inhibitor toolkit provides a rapid, inexpensive and simple means to assess the chemosensitivity of tumour cells and in conjunction with BH3 profiling offers much potential in personalising cancer therapy.
authors.affiliation: Departments of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GE, UK.|Department of Pharmacology, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Butterworth
authors.affiliation: Departments of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pettitt
authors.affiliation: Departments of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GE, UK.|Department of Pharmacology, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Shankar
authors.initials: S
authors.lastname: Varadarajan
authors.affiliation: Departments of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GE, UK.|Department of Pharmacology, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Cohen
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000032:analysis* / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C000603580:A-1331852; D000970:Antineoplastic Agents; C474007:Bax protein (53-86); D052160:Benzothiazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007546:Isoquinolines; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C579720:venetoclax