Advanced Materials Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China.
NanoPeptide (Qingdao) Biotechnology Ltd., Qingdao 266100, China.
ACS Biomater Sci Eng. 2022 Aug 8;8(8):3515-3525. doi: 10.1021/acsbiomaterials.2c00354. Epub 2022 Jun 13.
As an emerging technology in precision medicine, the patient-derived organoid (PDO) technology has been indicated to provide novel modalities to judge the sensitivity of individual tumors to cancer drugs. In this work, an model of colorectal cancer (CRC) was established using the PDO culture, and it is demonstrated that the PDO samples preserved, to a great extent, the histologic features and marker expression of the original tumor tissues. Subsequently, cancer drugs 5-FU, oxaliplatin, and irinotecan were selected and screened on five CRC PDO samples, while the patient-derived organoid xenograft (PDOX) model was applied for comparison. The receiver operating characteristic (ROC) curve was drawn according to the IC data from the PDO model and the relative tumor proliferation rate (T/C%) from PDOX. Interestingly, the area under the ROC curve was 0.84 (95% CI, 0.64-1.04, value = 0.028), which suggested that the IC of cancer drugs from the PDO model was strongly correlated with PDOX responses. In addition, the optimal sensitivity cutoff value for drug screening in CRC PDOs was identified at 10.35 μM, which could act as a reference value for efficacy evaluation of 5-FU, oxaliplatin, and irinotecan in the colorectal cancer drug screening. Since there are no unified criteria to judge the sensitivity of drugs , our work provides a method for establishing evaluation criteria via PDO and PDOX model using the patient tissues received from local hospitals, exhibiting potential in clinical cancer therapy and precision medicine.
作为精准医学领域的一项新兴技术，患者来源类器官（PDO）技术被证明为判断个体肿瘤对癌症药物敏感性提供了新方法。在这项工作中，我们使用 PDO 培养物建立了结直肠癌（CRC）模型，结果表明 PDO 样本在很大程度上保留了原始肿瘤组织的组织学特征和标志物表达。随后，我们选择了 5-FU、奥沙利铂和伊立替康这三种癌症药物在五个 CRC PDO 样本上进行筛选，并应用患者来源类器官异种移植（PDOX）模型进行比较。根据 PDO 模型的 IC 数据和 PDOX 的相对肿瘤增殖率（T/C%）绘制了受试者工作特征（ROC）曲线。有趣的是，ROC 曲线下面积为 0.84（95%CI，0.64-1.04，P 值=0.028），这表明 PDO 模型中癌症药物的 IC 与 PDOX 反应具有很强的相关性。此外，我们确定了 CRC PDO 中用于药物筛选的最佳敏感性截断值为 10.35 μM，该值可作为评估 5-FU、奥沙利铂和伊立替康在结直肠癌药物筛选中疗效的参考值。由于目前尚无统一的标准来判断药物的敏感性，我们的工作通过使用从当地医院获得的患者组织，为建立基于 PDO 和 PDOX 模型的评估标准提供了一种方法，这在临床癌症治疗和精准医学方面具有潜在的应用价值。
