2. Academic Validation
  3. A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations

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

  • Nat Commun. 2022 Nov 14;13(1):6944. doi: 10.1038/s41467-022-34627-5.
Hui Deng # 1 2 3,  Qian Lei # 4 5 6,  Chengdi Wang # 4,  Zhoufeng Wang 4 6,  Hai Chen 5 6,  Gang Wang 5,  Na Yang 5,  Dan Huang 7,  Quanwei Yu 5,  Mengling Yao 6,  Xue Xiao 6,  Guonian Zhu 6,  Cheng Cheng 6,  Yangqian Li 6,  Feng Li 7,  Panwen Tian 8,  Weimin Li 9 10 11
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. huideng0923@hotmail.com.
  • 2 Targeted Tracer Research and Development Laboratory, Precision Medicine Key Laboratory of Sichuan Province, Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. huideng0923@hotmail.com.
  • 3 Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. huideng0923@hotmail.com.
  • 4 Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 5 Targeted Tracer Research and Development Laboratory, Precision Medicine Key Laboratory of Sichuan Province, Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 6 Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 7 Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan, China.
  • 8 Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. mrascend@163.com.
  • 9 Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. weimi003@scu.edu.cn.
  • 10 Targeted Tracer Research and Development Laboratory, Precision Medicine Key Laboratory of Sichuan Province, Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. weimi003@scu.edu.cn.
  • 11 Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. weimi003@scu.edu.cn.
  • # Contributed equally.
PMID: 36376325 DOI: 10.1038/s41467-022-34627-5
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-152098
    基于EGFR-TKI的荧光探针
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