Aims　The　suboptimal　clinical　outcomes　of　pancreatic　ductal　adenocarcinoma(PDAC)　under　conventional　treatment　regimens　necessitate　investigations　into　ferroptosis　resistance　mechanisms.This　study　systematically　explores　molecular　determinants　underlying　ferroptosis　evasion　in　PDAC　malignancies.Methods　circRNA　sequencing　of　clinical　specimens　identified　ferroptosis-associated　circRNAs.Ferroptosis　progression　was　monitored　through　C11-BODIPY/FerroOrange　fluorescence,glutathione/malondialdehyde　quantification,and　ultrastructural　analysis　via　transmission　electron　microscopy.Molecular　interactomes　were　deciphered　using　RNA　pulldown-coupled　mass　spectrometry,RNA　immunoprecipitation,and　coimmunoprecipitation　assays.Therapeutic　validation　employed　HuNSG　mouse　xenograft　tumour　models.Results　CircRNA　sequencing　identified　cTRIP12　as　a　ferroptosis　resistance　mediator　in　PDAC　specimens.Genetic　silencing　of　cTRIP12　enhanced　tumor　cell　sensitivity　to　both　ferroptosis　inducers　and　immune　checkpoint　inhibitors.Mechanisticall...