biostudies-literatureLi DNational Natural Science Foundation of China17https://www.ebi.ac.uk/biostudies/studies/S-EPMC11756136biostudies-literatureUnknown13(1)<h4>Background</h4>Lung cancer, particularly non-small cell lung cancer (NSCLC), has high recurrence rates and remains a leading cause of cancer-related death, despite recent advances in its treatment. Emerging therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown promise but face significant challenges in targeting solid tumors. This study investigated the potential of combining receptor tyrosine kinase-like orphan receptor 1 (ROR1)-targeting CAR-T cells with ferroptosis inducers to promote ferroptosis of tumor cells and enhance anti-tumor efficacy.<h4>Methods</h4>RNA-seq data and immunofluorescence analysis of relapsed NSCLC patient samples were used to explore ROR1 expression. In addition, ROR1-targeting CAR-T cells were developed to assess cytotoxic activity agaBiomarker researchROR1 CAR-T cells and ferroptosis inducers orchestrate tumor ferroptosis via PC-PUFA2.PMC1175613682200245, 82104447, 82302641Liu HMa LLi DGuo WShan LLu CHou XWang JXie SZhang WWang RHuang ZWang YXu ZfalseROR1 CAR-T cells and ferroptosis inducers orchestrate tumor ferroptosis via PC-PUFA2.<h4>Background</h4>Lung cancer, particularly non-small cell lung cancer (NSCLC), has high recurrence rates and remains a leading cause of cancer-related death, despite recent advances in its treatment. Emerging therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown promise but face significant challenges in targeting solid tumors. This study investigated the potential of combining receptor tyrosine kinase-like orphan receptor 1 (ROR1)-targeting CAR-T cells with ferroptosis inducers to promote ferroptosis of tumor cells and enhance anti-tumor efficacy.<h4>Methods</h4>RNA-seq data and immunofluorescence analysis of relapsed NSCLC patient samples were used to explore ROR1 expression. In addition, ROR1-targeting CAR-T cells were developed to assess cytotoxic activity aga2025-01-01T00:00:00Z2025 Jan2026-06-02T07:11:17.008Z2025-04-05T00:25:37.376ZS-EPMC117561363984964510.1186/s40364-025-00730-0