HDS screening with patient-derived primary cells guided individualized therapy for esophageal squamous cell carcinoma- in vivo and vitro

Xing He; Hezhong Yan; Jie Hu; Xiaowei Duan; Mingjin Zhang; Haiqing Li; Jiaoxue Wang; Qian Gao; Senyuan Yu; Xilu Hou; Guobin Liao; Shicun Guo; Jin Li; Yurong Ge; Xiaolan Chen; Wenchao Wang; Jun Tang

doi:10.3389/fmed.2023.1212851

HDS screening with patient-derived primary cells guided individualized therapy for esophageal squamous cell carcinoma- in vivo and vitro

Front Med (Lausanne). 2023 Aug 2:10:1212851. doi: 10.3389/fmed.2023.1212851. eCollection 2023.

Authors

Xing He¹, Hezhong Yan¹, Jie Hu², Xiaowei Duan¹, Mingjin Zhang¹, Haiqing Li¹, Jiaoxue Wang¹, Qian Gao¹, Senyuan Yu¹, Xilu Hou¹, Guobin Liao¹, Shicun Guo¹, Jin Li¹, Yurong Ge¹, Xiaolan Chen¹, Wenchao Wang², Jun Tang¹

Affiliations

¹ Department of Gastroenterology, The 901th Hospital of Joint Logistics Support Force, Hefei, Anhui, China.
² Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.

Abstract

Objective: To analyze and evaluate the role of the High-throughput Drug Sensitivity (HDS) screening strategy in identifying highly sensitive drugs against esophageal squamous cell carcinoma (ESCC).

Methods: A total of 80 patients with progressive ESCC were randomly divided into the observation (40 cases) and the control groups (40 cases). In the observation group, primary ESCC cells were isolated from the tumor tissues with a gastroscope, and drug sensitivity screening was performed on cells derived from the 40 ESCC cases using the HDS method, followed by verification in a patient-derived tumor xenograft (PDX) mouse model. Finally, the differences in the therapeutic efficacy (levels of CEA, CYFRA21-1, SCCA after chemotherapy and the rates of overall survival, local progression, and distant metastasis at 12 months and 18 months time points after chemotherapy) were compared between the observation group (Screened drug-treated) and the control group (Paclitaxel combined with cisplatin regimen-treated).

Results: Forty ESCC patients were screened for nine different high-sensitive chemotherapeutics, with the majority showing sensitivity to Bortezomib. Experiments on animal models revealed that the tumor tissue mass of PDX mice treated with the HDS-screened drug was significantly lower than that of the Paclitaxel-treated mice (p < 0.05), and the therapeutic efficacy of the observation group was better than the control group (p < 0.05).

Conclusion: HDS screening technology can be beneficial in screening high-efficacy anticancer drugs for advanced-stage ESCC patients, thereby minimizing adverse drug toxicity in critically ill patients. Moreover, this study provides a new avenue for treating advanced ESCC patients with improved outcomes.

Keywords: drug sensitivity; esophageal squamous cell carcinoma; high-throughput drug sensitivity screening technology; patient-derived tumor xenografts; therapeutic efficacy.