title: [Molecules involved in apoptosis regulation as therapeutic targets in oncology].
abstract: Apoptosis is a programmed cellular death, a fast process (between four and six hours) in answer to a cellular stress. It involves a sequence of genetically determined intracellular events, allowing the inhibition of the main functions of the cell and its elimination by phagocytosis. The apoptosis inactivation is implied in tumours carcinogenesis. Although the tumour physiopathology implies a defect in activation-induced cell death, the treatment is designed to kill the transformed cells. The aim of this review is to describe the apoptotic mechanisms and to explain the interest of new therapeutic tools targeting apoptosis. Apoptosis is an orderly and synchronized process, regulated by two different pathways, the intrinsic way (mitochondrial) and extrinsic one (the death receptor). The targeting of apoptosis, a pathway intrinsically deficient in the tumor cells, is a potentially interesting strategy when the mechanism of its inhibition is well-identified. Small molecules targeting B-cell leukemia/lymphoma-2 (Bcl-2), inhibitor of apoptosis protein (IAPs) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors are currently under phase I/II studies, which show preliminary efficacy and safety. Their association with standard treatments seems an interesting therapeutic way in order to obtain a synergistic effect on tumor cell death.
authors.affiliation: CLCC François-Baclesse, service d'oncologie médicale, Caen, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lheureux
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Le Moulec
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053938:DNA Fragmentation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists
chemical_list: D000911:Antibodies, Monoclonal; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand