{"doi":"10.1101/2024.09.25.614990","title":"Second-Generation Cap Analogue Prodrugs for Targeting Aberrant Eukaryotic Translation Initiation Factor 4E (eIF4E) Activity in Drug-Resistant Melanoma","abstract":"ABSTRACT Melanoma is the deadliest form of skin cancer with a 5-year survival rate of less than 20%. While significant strides have been made in the field of kinase-targeted and immune-based therapies for melanoma, the development of resistance to these therapeutic agents has hindered the success of treatment. Drug-resistant melanoma is particularly reliant on enhanced cap-dependent translation to drive the production of oncoproteins that promote growth and survival. The m 7 GpppX cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) is the rate-limiting factor of cap-dependent translation initiation, and its overexpression in melanoma tumors has been shown to drive resistance to BRAF V600E kinase-targeted inhibitors. These findings point to eIF4E-targeted therapies as a promising strategy to overcome drug resistance in melanoma. Herein, we build upon our previous work of developing cell-permeable cap analogue inhibitors to design second-generation cap analogues that inhibit eIF4E-mediated cap-dependent translation in drug-resistant melanoma cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":503876,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":526988,"name":"Rachel L. O’Rourke","orcid":"0009-0002-1088-0307","position":1,"is_corresponding":false},{"id":406637,"name":"Arya Menon","orcid":"0000-0002-6925-4258","position":2,"is_corresponding":false},{"id":1354466,"name":"Gabriela Vega-Hernández","orcid":null,"position":3,"is_corresponding":false},{"id":613812,"name":"Jennifer L. Meagher","orcid":"0000-0003-1250-4575","position":4,"is_corresponding":false},{"id":613815,"name":"Jeanne A. Stuckey","orcid":"0000-0002-4192-8900","position":5,"is_corresponding":false},{"id":381288,"name":"Amanda L. Garner","orcid":"0000-0002-0870-3347","position":6,"is_corresponding":false},{"id":1051493,"name":"Emilio L. Cárdenas","orcid":null,"position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-19T02:10:35.597333Z","pmid":"39386734","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":[]}