Abstract 5765: Illuminating the kinase activity starmap in NSCLC via tyrosine phosphoproteomics

In lung cancer treatment, understanding kinase activity, particularly tyrosine phosphorylation, is crucial but incomplete. We studied tyrosine phosphoproteomics in 74 patients with non-small-cell lung cancer (NSCLC) using SH2-Superbinder and data-independent acquisition mass spectrometry. We identified 1,048 tyrosine phosphosites, the highest number reported in lung cancer research. We constructed a tyrosine phosphorylation starmap, enabling a novel and intuitive analysis of tumors versus normal adjacent tissues, revealing kinases driving tumor progression and metastasis. Subsequently, patients were stratified by kinase activity for multiple precision medicine perspectives. “Cold” and “hot” tumors were divided based on immune kinase activity, while cancer driver kinase profiling revealed vulnerability to BRD4 inhibitors in wild-type lung cancer cells. EGFR-L858R mutations benefited from combining MEK and EGFR inhibitors. Two distinct kinase activity panels predicted patient survival across different mutation backgrounds. Our findings underscore the diverse kinase activities in NSCLC and highlight the need for personalized therapy based on these profiles. Citation Format: Naizhong Zheng, Yi Liu, Jinfeng Yuan, Ying Hu, Yilin Wang, Tianhui Zhang, Aijuan Yu, Hui Zhou, Chao Zhou, Junjie Hou, Yinyin Xu, Xinxin Xu, Huan Ding, Yuxin Zhang, Rujie Zhong, Mengjie Yang, Chunyan Chang, Hongxuan Yan, Yuanyuan Shang, Weicong Ren, Shanshan Li, Hongdong Zhong, Yun Xiao, Zhang Zhang, Ming Han, Yu Pang. Illuminating the kinase activity starmap in NSCLC via tyrosine phosphoproteomics [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 5765.