title: The IAP Protein Family, SMAC Mimetics and Cancer Treatment.
abstract: Since the acquired resistance of cells to apoptosis is one of the major hallmarks of cancer, the endogenous inhibitors of apoptosis can be regarded as promising targets in the design of anticancer therapeutics. In addition to their antiapoptotic activity, inhibitor of apoptosis proteins (IAPs) are able to regulate numerous other cell functions, including proliferation, differentiation, and migration, as well as proinflammatory and immune responses. Study of the IAP family as target molecules in targeted therapies has recently focused on SMAC mimetics as synthetic IAP antagonists that have been under development as promising therapeutics. To overview the background of IAP proteins and to focus on the development of SMAC mimetics, the present review first looks at the mechanisms of IAP proteins' antiapoptotic activities and those for controlling those activities; then the SMAC mimetics, including birinapant, LCL161, and DEBIO1143/AT-406, and their clinical trials are introduced. To further clarify the processes to exert the efficacies of SMAC mimetics, it is necessary to determine therapeutic biomarkers that predict and assess them, which may include caspases and factors in the TNFα pathway.
authors.affiliation: R. E. Kavetsky Institute of Experimental Pathology, Oncology & Radiobiology Kyiv, Ukraine.
authors.forename: Alex
authors.initials: A
authors.lastname: Philchenkov
authors.affiliation: Department of Surgery, Miyagi Cancer Center, Natori, Miyagi, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Miura
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001392:Azocines / Q000494:pharmacology / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D051034:Inhibitor of Apoptosis Proteins / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001392:Azocines; D001559:Benzhydryl Compounds; D004151:Dipeptides; D007211:Indoles; D051034:Inhibitor of Apoptosis Proteins; C574246:LCL161; C559144:N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide; D013844:Thiazoles; C582429:birinapant