在小鼠中对迷你患者来源异种移植物的药物反应进行特征分析，以预测癌症患者的临床治疗反应。

BACKGROUND: Patient-derived organoids and xenografts (PDXs) have emerged as powerful models in functional diagnostics with high predictive power for anticancer drug response. However, limitations such as engraftment failure and time-consuming for establishing and expanding PDX models followed by testing drug efficacy, and inability to subject to systemic drug administration for ex vivo organoid culture hinder realistic and fast decision-making in selecting the right therapeutics in the clinic. The present study aimed to develop an advanced PDX model, namely MiniPDX, for rapidly testing drug efficacy to strengthen its value in personalized cancer treatment. METHODS: We developed a rapid in vivo drug sensitivity assay, OncoVee MiniPDX, for screening clinically relevant regimens for cancer. In this model, patient-derived tumor cells were arrayed within hollow fiber capsules, implanted subcutaneously into mice and cultured for 7 days. The cellular activity morphology and pharmacokinetics were systematically evaluated. MiniPDX performance (sensitivity, specificity, positive and negative predictive values) was examined using PDX as the reference. Drug responses were examined by tumor cell growth inhibition rate and tumor growth inhibition rate in PDX models and MiniPDX assays respectively. The results from MiniPDX were also used to evaluate its predictive power for clinical outcomes. RESULTS: Morphological and histopathological features of tumor cells within the MiniPDX capsules matched those both in PDX models and in original tumors. Drug responses in the PDX tumor graft assays correlated well with those in the corresponding MiniPDX assays using 26 PDX models generated from patients, including 14 gastric cancer, 10 lung cancer and 2 pancreatic cancer. The positive predictive value of MiniPDX was 92%, and the negative predictive value was 81% with a sensitivity of 80% and a specificity of 93%. Through expanding to clinical tumor samples, MiniPDX assay showed potential of wide clinical application. CONCLUSIONS: Fast in vivo MiniPDX assay based on capsule implantation was developed-to assess drug responses of both PDX tumor grafts and clinical cancer specimens. The high correlation between drug responses of paired MiniPDX and PDX tumor graft assay, as well as translational data suggest that MiniPDX assay is an advanced tool for personalized cancer treatment.

背景：患者来源的类器官和异种移植物（PDX）已成为功能诊断的强大模型，对癌症药物反应具有很高的预测能力。然而，建立和扩大 PDX 模型以及测试药物疗效所需的时间较长，同时也存在植入失败的问题，并且无法对类器官进行系统的药物给药进行离体培养，这阻碍了在临床上选择正确治疗方法的现实和快速决策。本研究旨在开发一种先进的 PDX 模型，即 MiniPDX，用于快速测试药物疗效，以增强其在个性化癌症治疗中的价值。

方法：我们开发了一种快速的体内药物敏感性测定法，OncoVee MiniPDX，用于筛选癌症的临床相关方案。在该模型中，患者来源的肿瘤细胞被排列在空心纤维胶囊内，皮下植入小鼠体内并培养 7 天。系统评估了细胞活性形态和药代动力学。使用 PDX 作为参考，检查了 MiniPDX 的性能（敏感性、特异性、阳性和阴性预测值）。通过肿瘤细胞生长抑制率和 PDX 模型和 MiniPDX 测定中的肿瘤生长抑制率分别检查药物反应。还使用 MiniPDX 的结果来评估其对临床结果的预测能力。

结果：MiniPDX 胶囊内的肿瘤细胞的形态学和组织病理学特征与 PDX 模型和原始肿瘤中的特征相匹配。使用 26 个来自患者的 PDX 模型生成的肿瘤移植测定中，药物反应与相应的 MiniPDX 测定中的药物反应密切相关，包括 14 个胃癌、10 个肺癌和 2 个胰腺癌。MiniPDX 的阳性预测值为 92%，阴性预测值为 81%，灵敏度为 80%，特异性为 93%。通过扩展到临床肿瘤样本，MiniPDX 测定显示出广泛的临床应用潜力。

结论：基于胶囊植入的快速体内 MiniPDX 测定法已被开发出来，用于评估 PDX 肿瘤移植和临床癌症标本的药物反应。配对的 MiniPDX 和 PDX 肿瘤移植测定中药物反应的高度相关性以及转化数据表明，MiniPDX 测定法是个性化癌症治疗的一种先进工具。