Targeted Drug-Loaded Chemical Probe Staining Assay to Predict Therapy Response and Function as an Independent Pathological Marker

• Published in: iScience 2019-11, Vol.21, p.549-561
• Main Authors: Zhang, Heng, Zhong, Wei-long, Sun, Bo, Yang, Guang, Liu, Yan-rong, Zhou, Bi-jiao, Chen, Xin, Jing, Xiang-yan, Huai, Long-cong, Liu, Ning, Zhang, Zhi-yuan, Li, Mi-mi, Han, Jing-xia, Qiao, Kai-liang, Meng, Jing, Zhou, Hong-gang, Chen, Shuang, Yang, Cheng, Sun, Tao
• Format: Article
• Language: English
• Subjects: Biochemical Assay; Drugs; Medical Biochemistry
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.10.050

Multi-targeted kinase inhibitors, such as sorafenib, have been used in various malignancies, but their efficacy in clinical applications varies among individuals and lacks pretherapeutic prediction measures. We applied the concept of “click chemistry” to pathological staining and established a drug-loaded probe staining assay. We stained the cells and different types of pathological sections and demonstrated that the assay was reliable. We further verified in cells, cell-derived xenograft model, and clinical level that the staining intensity of the probe could reflect drug sensitivity. The stained samples from 300 patients who suffered from hepatocellular carcinoma and used the sorafenib probe also indicated that staining intensity was closely related to clinical information and could be used as an independent marker without undergoing sorafenib therapy for prognosis. This assay provided new ideas for multi-target drug clinical trials, pre-medication prediction, and pathological research. [Display omitted] •The assay could be used for the rapid sensitivity detection of multi-target drugs•The assay could serve as an auxiliary technology for NGS and PDX•Sorafenib had multiple unknown primary contribution targets•Drug-probe staining could be used as an independent diagnostic and prognostic marker Drugs; Medical Biochemistry; Biochemical Assay