Time：4:00-5:30 PM，Monday, April 15，2024

    Host：Dr. Kunliang Guan, Chair Professor of School of Life Sciences

    Venue：Room E9-109, Yungu Campus

Speaker:

Dr. Hong-bin Ji, Professor , CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences

Dr. Hong-bin Ji focus on deciphering the molecular mechanisms of lung cancer initiation, phenotypic transition, metastasis, and developing novel therapeutic strategies to overcome drug resistance. 

Abstract:

KRASG12C inhibitors (adagrasib and sotorasib) have shown clinical promise in targeting KRASG12C-mutated lung cancers; however, most patients eventually develop resistance. In lung patients with adenocarcinoma with KRASG12C and STK11/LKB1 co-mutations, we find an enrichment of the squamous cell carcinoma gene signature in pre-treatment biopsies correlates with a poor response to adagrasib. Studies of Lkb1-deficient KRASG12C and KrasG12D lung cancer mouse models and organoids treated with KRAS inhibitors reveal tumors invoke a lineage plasticity program, adeno-to-squamous transition (AST), that enables resistance to KRAS inhibition. Transcriptomic and epigenomic analyses reveal ΔNp63 drives AST and modulates response to KRAS inhibition. We identify an intermediate high-plastic cell state marked by expression of an AST plasticity signature and Krt6a. Notably, expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.

联系人/Contact：

Wenyue Yu: yuwenyue@westlake.edu.cn

School of Life Sciences