Abstract 2987: Role of EIF4G1 network in non-small cell lung cancers (NSCLC) pathogenesis and development of targeted therapy

Abstract Although the Eukaryotic Translation Initiation Factor 4 Gamma 1 (EIF4G1) has been found overexpressed in a variety of cancers, its role in non-small cell lung cancers (NSCLC) pathogenesis, clinical relevance and therapeutic potential remain largely unknown. By using cancer patients tissue assays, our results indicate that EIF4G1 expressional levels are much higher in NSCLC tissues than in adjacent or normal lung tissues, which are also associated with NSCLC patient survival. By using an RNA-Sequencing based pipeline, the data show that EIF4G1 has a significant association with immune checkpoint molecules such as PD-1/PD-L1 in NSCLC. Protein array results identify the signature of proteins controlled by EIF4G1 in NSCLC cells, in which new candidates such as MUC1 and NRG1 are required for NSCLC survival and tumorigenesis with clinical relevance. EIF4G1 small-molecule inhibitors effectively repress NSCLC growth in cell culture and xenograft animal models. To further improve the specificity of EIF4G1 targeted therapies, we recently have designed and synthesized O’PROTAC-based EIF4G1 specific degraders which showing effective anti-NSCLC activities. Taken together, these results demonstrate the immunoregulatory functions, clinical relevance and therapeutic potential of the EIF4G1 network in NSCLC, which may represent a promising and novel target to improve lung cancer treatment. Citation Format: Zhiqiang Qin, Steven R. Post, Hong-yu Li, Lu Dai. Role of EIF4G1 network in non-small cell lung cancers (NSCLC) pathogenesis and development of targeted therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2987.