{"doi":"10.2147/dddt.s93545","title":"MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy","abstract":null,"journal":"Drug Design, Development and Therapy","year":2015,"id":621899,"datarank":0.5570358100056463,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.0,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1606184,"name":"Khiem Tran","orcid":null,"position":1,"is_corresponding":false},{"id":1454540,"name":"Michelle Cheng","orcid":"0000-0001-8399-5936","position":2,"is_corresponding":false},{"id":1606186,"name":"Anupam Mitra","orcid":null,"position":3,"is_corresponding":false},{"id":1606187,"name":"Hiromi Ogawa","orcid":null,"position":4,"is_corresponding":false},{"id":1606188,"name":"Vivian Shi","orcid":null,"position":5,"is_corresponding":false},{"id":283536,"name":"Laura Olney","orcid":null,"position":6,"is_corresponding":false},{"id":1502708,"name":"April Kloxin","orcid":null,"position":7,"is_corresponding":false},{"id":233183,"name":"Emanual Maverakis","orcid":"0000-0002-6294-6294","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy","abstract":"The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy.","is_dataset_classified":null,"base_score":3.713572066704308,"endowment":3.713572066704308,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26730180","pmcid":"PMC4694671","openalex_id":"https://openalex.org/W2219112405","authors":[],"funders":[],"total_grants":0,"fwci":2.894,"citation_percentile":0.91676083,"influential_citations":0,"citation_trend":[{"year":2016,"count":6},{"year":2017,"count":8},{"year":2018,"count":7},{"year":2019,"count":4},{"year":2020,"count":5},{"year":2021,"count":3},{"year":2023,"count":1},{"year":2024,"count":3},{"year":2025,"count":3}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://www.dovepress.com/getfile.php?fileID=28446","host_type":"journal"},{"url":"https://www.dovepress.com/getfile.php?fileID=28446","host_type":"publisher"},{"url":"https://doi.org/10.2147/dddt.s93545","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26730180","host_type":"repository"},{"url":"http://udspace.udel.edu/handle/19716/17698","host_type":"repository"},{"url":"https://doaj.org/article/55bac8097ae14a60b686c20a155273e6","host_type":"repository"},{"url":"https://www.dovepress.com/mek-inhibitors-and-their-potential-in-the-treatment-of-advanced-melano-peer-reviewed-article-DDDT","host_type":"repository"},{"url":"https://escholarship.org/uc/item/78j206jc","host_type":"repository"},{"url":"http://doi.org/10.2147/DDDT.S93545","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4694671","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4694671?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Melanoma and MAPK Pathways","Synthesis of Tetrazole Derivatives","Cancer Mechanisms and Therapy"],"mesh_terms":["Antineoplastic Combined Chemotherapy Protocols","Humans","Melanoma","Skin Neoplasms","Mitogen-Activated Protein Kinase Kinases","Protein Kinase Inhibitors","Molecular Targeted Therapy"],"keywords":["Dabrafenib","Vemurafenib","Trametinib","Melanoma","MEK inhibitor","Medicine","MAPK/ERK pathway","Cancer research","Targeted therapy","Combination therapy","Metastatic melanoma","Kinase","Pharmacology","Internal medicine","Cancer","Biology","Mapk Pathway","Braf Inhibitor","Cobimetinib"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T16:40:54.248589Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}