{"doi":"10.1016/j.ebiom.2024.105356","title":"Customised design of antisense oligonucleotides targeting EGFR driver mutants for personalised treatment of non-small cell lung cancer","abstract":null,"journal":"eBioMedicine","year":2024,"id":631355,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"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":1636108,"name":"Cao Dai Phung","orcid":null,"position":1,"is_corresponding":false},{"id":1636109,"name":"Brendon Z.J. Yeo","orcid":null,"position":2,"is_corresponding":false},{"id":1636110,"name":"Rebecca C. Prajogo","orcid":"0009-0005-8578-8603","position":3,"is_corresponding":false},{"id":1636111,"name":"Migara K. Jayasinghe","orcid":null,"position":4,"is_corresponding":false},{"id":1636112,"name":"Ju Yuan","orcid":null,"position":5,"is_corresponding":false},{"id":545854,"name":"Daniel S.W. Tan","orcid":"0000-0002-6514-6786","position":6,"is_corresponding":false},{"id":1636113,"name":"Eric Y.M. Yeo","orcid":null,"position":7,"is_corresponding":false},{"id":816875,"name":"Boon Cher Goh","orcid":"0000-0002-4107-102X","position":8,"is_corresponding":false},{"id":424240,"name":"Wai Leong Tam","orcid":"0000-0003-2365-5264","position":9,"is_corresponding":false},{"id":558796,"name":"Minh T. N. Le","orcid":"0000-0002-6077-1566","position":10,"is_corresponding":false},{"id":1636107,"name":"Trinh T.T. Tran","orcid":"0000-0003-1938-6954","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Customised design of antisense oligonucleotides targeting EGFR driver mutants for personalised treatment of non-small cell lung cancer","abstract":"BACKGROUND: Tyrosine kinase inhibitors (TKIs) are currently the standard therapy for patients with non-small cell lung cancer (NSCLC) bearing mutations in epidermal growth factor receptor (EGFR). Unfortunately, drug-acquired resistance is inevitable due to the emergence of new mutations in EGFR. Moreover, the TKI treatment is associated with severe toxicities due to the unspecific inhibition of wild-type (WT) EGFR. Thus, treatment that is customised to an individual's genetic alterations in EGFR may offer greater therapeutic benefits for patients with NSCLC. METHODS: In this study, we demonstrate a new therapeutic strategy utilising customised antisense oligonucleotides (ASOs) to selectively target activating mutations in the EGFR gene in an individualised manner that can overcome drug-resistant mutations. We use extracellular vesicles (EVs) as a vehicle to deliver ASOs to NSCLC cells. FINDINGS: Specifically guided by the mutational profile identified in NSCLC patients, we have successfully developed ASOs that selectively inhibit point mutations in the EGFR gene, including L858R and T790M, while sparing the WT EGFR. Delivery of the EGFR-targeting ASOs by EVs significantly reduced tumour growth in xenograft models of EGFR-L858R/T790M-driven NSCLC. Importantly, we have also shown that EGFR-targeting ASOs exhibit more potent anti-cancer effect than TKIs in NSCLC with EGFR mutations, effectively suppressing a patient-derived TKI-resistant NSCLC tumour. INTERPRETATION: Overall, by harnessing the specificity and efficacy of ASOs, we present an effective and adaptable therapeutic platform for NSCLC treatment. FUNDING: This study was funded by Singapore's Ministry of Health (NMRC/OFIRG/MOH-000643-00, OFIRG21nov-0068, NMRC/OFLCG/002-2018, OFYIRG22jul-0034), National Research Foundation (NRF-NRFI08-2022, NRF-CRP22-2019-0003, NRF-CRP23-2019-0004), A∗STAR, and Ministry of Education.","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39303667","pmcid":"PMC11437961","openalex_id":"https://openalex.org/W4402636257","authors":[],"funders":[{"funder_name":"National Research Foundation of Singapore","grant_id":"NRF-CRP23-2019-0004","title":null},{"funder_name":"National Research Foundation of Singapore","grant_id":"NRF-NRFI08-2022","title":null},{"funder_name":"National Research Foundation of Singapore","grant_id":"NRF-CRP22-2019-0003","title":null},{"funder_name":"National Medical Research Council","grant_id":"NMRC/OFLCG/002-2018","title":null},{"funder_name":"National Medical Research Council","grant_id":"NMRC/OFIRG/ MOH-000643-00","title":null},{"funder_name":"National Medical Research Council","grant_id":"OFYIRG22jul-0034","title":null},{"funder_name":"National Medical Research Council","grant_id":"OFIRG21nov-0068","title":null},{"funder_name":"Ministry of Health -Singapore","grant_id":"","title":null},{"funder_name":"Agency for Science, Technology and Research","grant_id":"","title":null},{"funder_name":"Ministry of Education - Singapore","grant_id":"","title":null}],"total_grants":10,"fwci":3.394,"citation_percentile":0.93496867,"influential_citations":0,"citation_trend":[{"year":2025,"count":9},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://doi.org/10.1016/j.ebiom.2024.105356","host_type":"journal"},{"url":"https://doi.org/10.1016/j.ebiom.2024.105356","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S235239642400392X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S235239642400392X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39303667","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11437961","host_type":"repository"},{"url":"https://doaj.org/article/e26bce2e85fd4ec6899f1442ffa2a9fc","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11437961/pdf/main.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11437961","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11437961?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Lung Cancer Treatments and Mutations","Extracellular vesicles in disease","Lung Cancer Research Studies","Carcinoma, Non-Small-Cell Lung","Humans","ErbB Receptors","Oligonucleotides, Antisense","Lung Neoplasms","Animals","Mutation","Mice","Cell Line, Tumor","Xenograft Model Antitumor Assays","Precision Medicine","Drug Resistance, Neoplasm","Extracellular Vesicles","Disease Models, Animal","Protein Kinase Inhibitors","Antineoplastic Agents"],"mesh_terms":["Extracellular Vesicles","Animals","Antineoplastic Agents","Carcinoma, Non-Small-Cell Lung","Disease Models, Animal","Humans","Lung Neoplasms","Mutation","Oligonucleotides, Antisense","Drug Resistance, Neoplasm","Xenograft Model Antitumor Assays","Cell Line, Tumor","Protein Kinase Inhibitors","Mice","Precision Medicine","ErbB Receptors"],"keywords":["Oligonucleotide","Mutant","Cancer research","Lung cancer","Medicine","Cell","Computational biology","Biology","Gene","Oncology","Genetics","EGFR","Antisense oligonucleotides","Cancer therapy","Non-small cell lung cancer","Extracellular Vesicles"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"cellosaurus"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T23:24:39.204065Z","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":[]}