{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vahabi M"],"funding":["Fondazione AIRC per la ricerca sul cancro ETS"],"pagination":["217"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12288264"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(1)"],"pubmed_abstract":["<h4>Background</h4>Nucleoside analogues are crucial in treating non-small cell lung cancer (NSCLC), but resistance hampers patient outcomes. The cytidine analogue RX-3117 shows promise in gemcitabine-resistant cancers, yet mechanisms underlying acquired resistance to this drug remain unexplored. This study includes a comprehensive investigation into RX-3117 resistance mechanisms by leveraging new preclinical models and cutting-edge genomic tools, including a CRISPR-Cas9 knockout screen and transcriptomics.<h4>Methods</h4>NSCLC cell lines A549 and SW1573 were exposed to stepwise increasing concentrations of RX-3117 to establish stable resistant subclones, confirmed by SRB and clonogenic assays. Intracellular RX-3117 nucleotide levels were measured via LC/MS-MS, prompting the evaluation and "],"journal":["Journal of experimental & clinical cancer research : CR"],"pubmed_title":["Unraveling resistance mechanisms to the novel nucleoside analog RX-3117 in lung cancer: insights into DNA repair, cell cycle dysregulation and targeting PKMYT1 for improved therapy."],"pmcid":["PMC12288264"],"funding_grant_id":["IG 24444"],"pubmed_authors":["Lencioni G","Strano S","Wang B","Vahabi M","Giovannetti E","Blandino G","Sarkisjan D","Donati V","Xu G","Hassouni BE","Honeywell RJ","Deng D","Mantini G","Peters GJ"],"additional_accession":[]},"is_claimable":false,"name":"Unraveling resistance mechanisms to the novel nucleoside analog RX-3117 in lung cancer: insights into DNA repair, cell cycle dysregulation and targeting PKMYT1 for improved therapy.","description":"<h4>Background</h4>Nucleoside analogues are crucial in treating non-small cell lung cancer (NSCLC), but resistance hampers patient outcomes. The cytidine analogue RX-3117 shows promise in gemcitabine-resistant cancers, yet mechanisms underlying acquired resistance to this drug remain unexplored. This study includes a comprehensive investigation into RX-3117 resistance mechanisms by leveraging new preclinical models and cutting-edge genomic tools, including a CRISPR-Cas9 knockout screen and transcriptomics.<h4>Methods</h4>NSCLC cell lines A549 and SW1573 were exposed to stepwise increasing concentrations of RX-3117 to establish stable resistant subclones, confirmed by SRB and clonogenic assays. Intracellular RX-3117 nucleotide levels were measured via LC/MS-MS, prompting the evaluation and ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-03-10T23:05:55.735Z","creation":"2025-08-12T03:05:01.635Z"},"accession":"S-EPMC12288264","cross_references":{"pubmed":["40702552"],"doi":["10.1186/s13046-025-03470-z"]}}