title: Trametinib in metastatic melanoma.
abstract: The treatment of metastatic melanoma is rapidly changing. In 2002, the BRAF mutation was described in over 50% of melanomas and led to the first BRAF inhibitor, vemurafenib, being approved for clinical use in 2011. Clinical responses are often rapid but duration of response is limited due to the development of resistance. MEK is the next downstream target from BRAF in the MAP kinase pathway. Trametinib was the first MEK inhibitor to be approved for clinical use in 2013. Preclinical studies demonstrated a delay in resistance and a reduction in cutaneous toxicity by combined BRAF and MEK inhibition. Here, we review the rationale for clinical development of trametinib and give an update on recent clinical trials of trametinib alone and in combination with braf inhibition in melanoma.
authors.affiliation: Mount Vernon Hospital, Medical Oncology, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK.
authors.forename: Neha
authors.initials: N
authors.lastname: Chopra
authors.forename: Paul D
authors.initials: PD
authors.lastname: Nathan
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D011728:Pyridones / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human
keywords: BRAF inhibitor; MEK inhibitor; medical oncology; melanoma; trametinib