{"doi":"10.1016/j.celrep.2024.114134","title":"The MYCN 5′ UTR as a therapeutic target in neuroblastoma","abstract":"Tumor MYCN amplification is seen in high-risk neuroblastoma, yet direct targeting of this oncogenic transcription factor has been challenging. Here, we take advantage of the dependence of MYCN-amplified neuroblastoma cells on increased protein synthesis to inhibit the activity of eukaryotic translation initiation factor 4A1 (eIF4A1) using an amidino-rocaglate, CMLD012824. Consistent with the role of this RNA helicase in resolving structural barriers in 5' untranslated regions (UTRs), CMLD012824 increased eIF4A1 affinity for polypurine-rich 5' UTRs, including that of the MYCN and associated transcripts with critical roles in cell proliferation. CMLD012824-mediated clamping of eIF4A1 spanned the full lengths of mRNAs, while translational inhibition was mediated through 5' UTR binding in a cap-dependent and -independent manner. Finally, CMLD012824 led to growth inhibition in MYCN-amplified neuroblastoma models without generalized toxicity. Our studies highlight the key role of eIF4A1 in MYCN-amplified neuroblastoma and demonstrate the therapeutic potential of disrupting its function.","journal":"Cell Reports","year":2024,"id":448558,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"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":275156,"name":"Lauren E. Brown","orcid":"0000-0001-9489-484X","position":1,"is_corresponding":false},{"id":1267504,"name":"Ushashi Banerjee","orcid":"0000-0002-8515-1910","position":2,"is_corresponding":false},{"id":31863,"name":"Ruben Dries","orcid":"0000-0001-7650-7754","position":3,"is_corresponding":false},{"id":357174,"name":"Bandana Sharma","orcid":null,"position":4,"is_corresponding":false},{"id":449877,"name":"Alyssa L. Kennedy","orcid":"0000-0001-7948-5933","position":5,"is_corresponding":false},{"id":275161,"name":"John A. Porco","orcid":"0000-0002-2991-5680","position":6,"is_corresponding":false},{"id":267026,"name":"Rani E. George","orcid":"0000-0003-4206-1779","position":7,"is_corresponding":false},{"id":895031,"name":"Marina P. Volegova","orcid":"0000-0003-1209-4334","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:02:12.215092Z","pmid":"38662542","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":[]}