He Xing, Yan Hezhong, Hu Jie, Duan Xiaowei, Zhang Mingjin, Li Haiqing, Wang Jiaoxue, Gao Qian, Yu Senyuan, Hou Xilu, Liao Guobin, Guo Shicun, Li Jin, Ge Yurong, Chen Xiaolan, Wang Wenchao, Tang Jun
Department of Gastroenterology, The 901th Hospital of Joint Logistics Support Force, Hefei, Anhui, China.
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.
Front Med (Lausanne). 2023 Aug 2;10:1212851. doi: 10.3389/fmed.2023.1212851. eCollection 2023.
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).
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).
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 ( < 0.05), and the therapeutic efficacy of the observation group was better than the control group ( < 0.05).
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.
分析和评估高通量药物敏感性（HDS）筛选策略在识别针对食管鳞状细胞癌（ESCC）的高敏感性药物中的作用。
将80例进展期ESCC患者随机分为观察组（40例）和对照组（40例）。观察组采用胃镜从肿瘤组织中分离出原发性ESCC细胞，使用HDS方法对40例ESCC病例来源的细胞进行药物敏感性筛选，随后在患者来源的肿瘤异种移植（PDX）小鼠模型中进行验证。最后，比较观察组（筛选药物治疗）和对照组（紫杉醇联合顺铂方案治疗）之间化疗疗效的差异（化疗后CEA、CYFRA21-1、SCCA水平以及化疗后12个月和18个月时间点的总生存、局部进展和远处转移率）。
对40例ESCC患者筛选出9种不同的高敏感性化疗药物，大多数对硼替佐米敏感。动物模型实验显示，用HDS筛选药物治疗的PDX小鼠的肿瘤组织块明显低于紫杉醇治疗的小鼠（<0.05），观察组的治疗效果优于对照组（<0.05）。
HDS筛选技术有助于为晚期ESCC患者筛选高效抗癌药物，从而将重症患者的药物毒性降至最低。此外，本研究为治疗晚期ESCC患者提供了一条改善预后的新途径。
