Zebrafish patient-derived xenografts accurately and quickly reproduce treatment outcomes in non–small cell lung cancer patients

Abstract

Zebrafish patient-derived xenograft (zPDX) models have shown great potential in predicting the short-term treatment response in various types of tumor cases. However, few studies have used zPDX models for drug screening in non–small cell lung cancer (NSCLC). We aimed to compare the treatment responses of patients with NSCLC with those of the corresponding zPDX models. Tumor cells were obtained from pleural fluid or biopsy procedures from patients with NSCLC and injected into the perivitelline space of zebrafish larvae. Then, the same antineoplastic drugs administered to the corresponding patient were tested in the successfully constructed zPDX model, for 3 days. Responses to treatment were compared. A total of 21 patients with advanced NSCLC were enrolled in our study, and 13 corresponding zPDX models were successfully established. Based on the clinical medication of enrolled patients, we provided a corresponding drug treatment to these zebrafish embryos, including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), pemetrexed/platinum (AP), or docetaxel/platinum (DP) administration. The chemosensitivity consistency rate between the clinical responses and those obtained from zPDXs was 76.9% (10/13). There was a high correlation between patient responses and the corresponding zPDX drug responses. Thus, zPDX can accurately and quickly reproduce patient responses to treatment with EGFR TKIs, AP, and DP and has a considerable potential to serve as a biological platform for predicting treatment effect on patients with NSCLC.