title: New dimension in therapeutic targeting of BCL-2 family proteins.
abstract: Proteins of the BCL-2 family control the mitochondrial pathway of apoptosis. Targeting these proteins proves to be an attractive strategy for anticancer therapy. The biological context is based on the fact that BH3-only members of the family are specific antagonists of prosurvival members. This prompted the identification of "BH3 mimetic" compounds. These small peptides or organic molecules indeed mimic the BH3 domain of BH3-only proteins: by selectively binding and antagonizing prosurvival proteins, they can induce apoptosis in malignant cells. Some small-molecule inhibitors of prosurvival proteins have already entered clinical trials in cancer patients and two of them have shown significant therapeutic effects. The latest developments in the field of targeting BCL-2 family proteins highlight several new antagonists of prosurvival proteins as well as direct activators of proapoptotic proteins. These compounds open up novel prospects for the development of BH3 mimetic anticancer drugs.
authors.affiliation: INSERM U 965, Hôpital Lariboisière, Paris, France.|Université Paris Diderot, UMR S965, Paris, France.
authors.forename: Samaher
authors.initials: S
authors.lastname: Besbes
authors.affiliation: INSERM U 965, Hôpital Lariboisière, Paris, France.|Université Paris Diderot, UMR S965, Paris, France.
authors.forename: Massoud
authors.initials: M
authors.lastname: Mirshahi
authors.affiliation: INSERM U 965, Hôpital Lariboisière, Paris, France.|Université Paris Diderot, UMR S965, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pocard
authors.affiliation: INSERM U 965, Hôpital Lariboisière, Paris, France.|Université Paris Diderot, UMR S965, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Billard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D040761:Biomimetic Materials / Q000494:pharmacology; D006801:Humans; D058990:Molecular Targeted Therapy; D010446:Peptide Fragments / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C474007:Bax protein (53-86); D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: BH3 mimetics; anticancer therapy; apoptosis; prosurvival protein antagonists; targeting BCL-2 family proteins