BCL-2 family antagonists for cancer therapy.
Overexpression of members of the BCL-2 family of pro-survival proteins is commonly associated with unfavourable pathogenesis in cancer. The convergence of cytotoxic stress signals on the extended BCL-2 protein family provides the biological rationale for directly targeting this family to induce apoptotic cell death. Recently, several compounds have been described that inhibit the interaction between BCL-2 family members and their natural ligand, a helical peptide sequence known as the BH3 domain. Here, we review preclinical and clinical data on these compounds, and recommend four criteria that define antagonists of the BCL-2 protein family.
Lessene
Guillaume
G
Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. glessene@wehi.edu.au
Czabotar
Peter E
PE
Colman
Peter M
PM
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics; D023421:Models, Animal; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011487:Protein Conformation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000187:drug effects
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein