Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing 100191, China.
Department of General Surgery, Peking University Third Hospital, Beijing 100191, China.
Biomed Pharmacother. 2023 Jul;163:114751. doi: 10.1016/j.biopha.2023.114751. Epub 2023 Apr 26.
Gastric cancer treatment is complicated by the molecular heterogeneity of human tumor cells, which limits the efficacy of standard therapy and necessitates the need for personalized treatment development. Patient-derived organoids (PDOs) are promising preclinical cancer models, exhibiting high clinical efficacy in predicting drug sensitivity, thus providing a new means for personalized precision medicine.
PDOs were established from surgically resected gastric cancer tumor tissues. Molecular characterization of the tumor tissues and PDOs was performed using whole-exome sequencing analysis. Drug sensitivity tests were performed by treating the PDO cultures with 21 standard-of-care drugs corresponding to patient treatment. We evaluated whether the PDO drug phenotype reflects the corresponding patient's treatment response by comparing the drug sensitivity test results with clinical data.
Twelve PDOs that satisfied the drug sensitivity test criteria were successfully constructed. PDOs closely recapitulated the pathophysiology and genetic changes in the corresponding tumors, and exhibited different sensitivities to the tested drugs. In one clinical case study, the PDO accurately predicted the patient's sensitivity to capecitabine and oxaliplatin, and in a second case study the PDO successfully predicted the patient's insensitivity to S-1 chemotherapy. In summary, six of the eight cases exhibited consistency between PDO drug susceptibility test results and the clinical response of the matched patient.
PDO drug sensitivity tests can predict the clinical response of patients with gastric cancer to drugs, and PDOs can therefore be used as a preclinical platform to guide the development of personalized cancer treatment.
胃癌的治疗受到人类肿瘤细胞分子异质性的限制，这降低了标准疗法的疗效，因此需要开发个性化治疗方法。患者来源的类器官（PDO）是很有前景的临床前癌症模型，在预测药物敏感性方面显示出较高的临床疗效，为个性化精准医学提供了新的手段。
从手术切除的胃癌肿瘤组织中建立 PDO。使用全外显子组测序分析对肿瘤组织和 PDO 进行分子特征分析。通过用 21 种标准治疗药物处理 PDO 培养物来进行药物敏感性测试，这些药物对应患者的治疗方案。我们通过将药物敏感性测试结果与临床数据进行比较，评估 PDO 药物表型是否反映了相应患者的治疗反应。
成功构建了 12 个符合药物敏感性测试标准的 PDO。PDO 紧密重现了相应肿瘤的病理生理学和遗传变化，并对测试药物表现出不同的敏感性。在一个临床案例研究中，PDO 准确预测了患者对卡培他滨和奥沙利铂的敏感性，在另一个案例研究中，PDO 成功预测了患者对 S-1 化疗的不敏感性。总的来说，8 个病例中有 6 个在 PDO 药物敏感性测试结果和匹配患者的临床反应之间表现出一致性。
PDO 药物敏感性测试可以预测胃癌患者对药物的临床反应，因此 PDO 可以作为一个临床前平台来指导个性化癌症治疗的开发。
