title: ERK pathway inhibitors: how low should we go?
abstract: Resistance to RAF inhibitors is generally accompanied by reactivation of extracellular signal-regulated kinase (ERK) signaling. SCH772984, a selective, ATP-competitive inhibitor of ERK1 and ERK2, is effective in BRAF-mutant models in which resistance is the result of ERK reactivation. SCH772984 may also have a role in the treatment of tumors in which ERK is dysregulated by mutant RAS, NF1, or activated receptor tyrosine kinases, settings in which current RAF inhibitors are ineffective.
authors.affiliation: Louis V. Gerstner, Jr. Sloan-Kettering Graduate School of Biomedical Sciences, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Moriah H
authors.initials: MH
authors.lastname: Nissan
authors.forename: Neal
authors.initials: N
authors.lastname: Rosen
authors.forename: David B
authors.initials: DB
authors.lastname: Solit
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007191:Indazoles / Q000494:pharmacology*; D007211:Indoles / Q000627:therapeutic use; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010091:Oximes / Q000627:therapeutic use; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D010091:Oximes; D010879:Piperazines; D047428:Protein Kinase Inhibitors; C587178:SCH772984; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib