title: BH3-only proteins: possible proapoptotic triggers for melanoma therapy.
abstract: Despite recent developments for new targeted therapies in melanoma, as BRAF inhibitors and immune-stimulating antibodies, tumor relapse frequently follows within less than a year. Therapy resistance is explained by defects in proapoptotic signalling. Thus, efficient induction of apoptosis in tumor cells appears as predominant therapeutic goal. In apoptosis control of melanoma, the balance between pro- and antiapoptotic Bcl-2 proteins plays a decisive role. In particular, members of the subfamily of BH3-only proteins function as proapoptotic triggers, and mimetics of these proteins are already in clinical trials in other cancers. Recent experimental work has revealed that the effects of different treatments in melanoma are related to the activation of BH3-only proteins, and also the proapoptotic effects of BRAF inhibitors are prevented by knockdown of the BH3-only protein Bim. Thus, melanoma therapy might be critically improved by the combination of survival pathway antagonists as BRAF inhibitors with BH3 mimetics.
authors.affiliation: Department of Dermatology, Venerology and Allergology, HTCC - Skin Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Plötz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Eberle
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D011518:Proto-Oncogene Proteins / Q000502:physiology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C581062:RTL10 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Bcl-2 homology domain 3; Bcl-2 proteins; Bim; apoptosis; melanoma