title: Combination of RAF and MEK inhibition for the treatment of BRAF-mutated melanoma: feedback is not encouraged.
abstract: In BRAF V600E melanoma patients, RAF inhibitor treatment causes a MEK-inhibitor-sensitive, RAF-inhibitor-resistant adaptive reactivation of ERK signaling. In clinical trials combining MEK and RAF inhibitors, therapeutic efficacy was modestly enhanced, suggesting the utility of inhibiting feedback-reactivated pathways. Strategies for optimally inhibiting ERK signaling should be explored.
authors.affiliation: Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: chapmanp@mskcc.org.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Chapman
authors.affiliation: Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Solit
authors.affiliation: Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Rosen
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D025461:Feedback, Physiological; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D058990:Molecular Targeted Therapy; D020125:Mutation, Missense; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020930:MAP Kinase Kinase Kinases