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lüll Targeting the Bcl-2-regulated apoptosis pathway by BH3 mimetics: a breakthrough in anticancer therapy?Labi V; Grespi F; Baumgartner F; Villunger ACell Death Differ 2008[Jun]; 15 (6): 977-87Induction of apoptosis in tumor cells by direct activation of the Bcl-2-regulated apoptosis pathway by small molecule drugs carries high hopes to overcome the shortcomings of current anticancer therapies. This novel therapy concept builds on emerging insights into how Bcl-2-like molecules maintain mitochondrial integrity and how pro-apoptotic BH3-only proteins lead to its disruption. Means to unleash the pro-apoptotic potential of BH3-only proteins in tumor cells, or to bypass the need for BH3-only proteins by directly blocking possible interactions of Bcl-2-like pro-survival molecules with Bax and/or Bak, constitute interesting options for the design of novel anticancer therapies. For the optimization and clinical implementation of these novel anticancer strategies, a detailed understanding of the role of individual BH3-only proteins in cell death signaling in healthy cells and during tumor suppression is required. In this review, we will touch on the latest findings on BH3-only protein function and attempts to define the molecular properties of the so-called 'BH3 mimetics,' a novel class of anticancer agents, able to prompt apoptosis in tumor cells, regardless of their p53 or Bcl-2 status.|*Apoptosis[MESH]|Antineoplastic Agents/chemistry/pharmacology/*therapeutic use[MESH]|Biphenyl Compounds/chemistry/pharmacology/*therapeutic use[MESH]|Drug Resistance, Neoplasm[MESH]|Humans[MESH]|Molecular Mimicry[MESH]|Neoplasms/*drug therapy[MESH]|Nitrophenols/chemistry/pharmacology/*therapeutic use[MESH]|Piperazines/chemistry/pharmacology/therapeutic use[MESH]|Protein Structure, Tertiary[MESH]|Proto-Oncogene Proteins c-bcl-2/*antagonists & inhibitors/chemistry/physiology[MESH]|Signal Transduction[MESH]|Sulfonamides/chemistry/pharmacology/*therapeutic use[MESH] |