A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations

Hui Deng (), Qian Lei, Chengdi Wang, Zhoufeng Wang, Hai Chen, Gang Wang, Na Yang, Dan Huang, Quanwei Yu, Mengling Yao, Xue Xiao, Guonian Zhu, Cheng Cheng, Yangqian Li, Feng Li, Panwen Tian () and Weimin Li ()
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Hui Deng: Sichuan University
Qian Lei: Sichuan University
Chengdi Wang: Sichuan University
Zhoufeng Wang: Sichuan University
Hai Chen: Sichuan University
Gang Wang: Sichuan University
Na Yang: Sichuan University
Dan Huang: Sichuan University
Quanwei Yu: Sichuan University
Mengling Yao: Sichuan University
Xue Xiao: Sichuan University
Guonian Zhu: Sichuan University
Cheng Cheng: Sichuan University
Yangqian Li: Sichuan University
Feng Li: Sichuan University
Panwen Tian: Sichuan University
Weimin Li: Sichuan University

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Therapeutic responses of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) are known to be associated with EGFR mutations. However, a proportion of NSCLCs carrying EGFR mutations still progress on EGFR-TKI underlining the imperfect correlation. Structure-function-based approaches have recently been reported to perform better in retrospectively predicting patient outcomes following EGFR-TKI treatment than exon-based method. Here, we develop a multicolor fluorescence-activated cell sorting (FACS) with an EGFR-TKI-based fluorogenic probe (HX103) to profile active-EGFR in tumors. HX103-based FACS shows an overall agreement with gene mutations of 82.6%, sensitivity of 81.8% and specificity of 83.3% for discriminating EGFR-activating mutations from wild-type in surgical specimens from NSCLC patients. We then translate HX103 to the clinical studies for prediction of EGFR-TKI sensitivity. When integrating computed tomography imaging with HX103-based FACS, we find a high correlation between EGFR-TKI therapy response and probe labeling. These studies demonstrate HX103-based FACS provides a high predictive performance for response to EGFR-TKI, suggesting the potential utility of an EGFR-TKI-based probe in precision medicine trials to stratify NSCLC patients for EGFR-TKI treatment.

Date: 2022
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DOI: 10.1038/s41467-022-34627-5

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