Background:Patient-derived advanced prostate cancer organoids have been developed to mimic tumor heterogeneity and beneficially predict optimized drugs for specific patients. The organoids are promising functional drug screening models which can capture patient outcomes. However, organoid development from transurethral resection of the prostate (TUR-P) has been hampered by a low success rate, and the cost of culture should be reduced for realistically clinical settings. In our study, we aimed to improve the success rate and reduce the cost of establishing advanced prostate cancer organoids from TUR-P specimens.Methods:We optimized and improved both the organoid culture protocol and the fetal bovine serum (FBS) based-organoid culture medium, which is suitable for performing drug testing in a short turnaround time. To confirm that the generated organoids could recapitulate the tumor heterogeneity of original tissues, the organoids were validated with histological, immunohistochemical, and genomic analyses.Results:Following the optimized protocol, we successfully generated organoids in approximately 18 out of 29 cases (or 62.07%), which exhibited effective growth and survival. In addition, we found that the established organoids efficiently identified and captured tumor characteristics present in their matched original tissues, as indicated by histological, immunohistochemical, and comprehensive genomic analysis. As a proof of concept for personalized medicine, the generated organoids were treated with anti-cancer drugs, including docetaxel and enzalutamide in parallel with the clinical treatments. Interestingly, the in vitro drug screening results were positively correlated with the patient outcomes at the clinical level.Conclusions:Taken together, the established APC organoids were able to precisely predict patients’ outcomes for treatment decision-making within a month in a cost-effective manner.
背景：患者来源的晚期前列腺癌类器官已被开发用于模拟肿瘤异质性，并有助于为特定患者预测优化药物。这类器官作为功能性药物筛选模型具有广阔前景，能够反映患者的治疗反应。然而，经尿道前列腺切除术（TUR-P）标本构建类器官的成功率较低，且培养成本需降低以适应实际临床应用。本研究旨在提高TUR-P标本构建晚期前列腺癌类器官的成功率并降低培养成本。 方法：我们优化改进了类器官培养方案及基于胎牛血清（FBS）的类器官培养基，使其适用于短周期药物测试。为验证所构建类器官能否重现原始组织的肿瘤异质性，我们通过组织学、免疫组化和基因组学分析对类器官进行了系统验证。 结果：采用优化方案后，29例样本中成功构建类器官约18例（成功率62.07%），类器官表现出良好的生长活性和存活率。组织学、免疫组化及综合基因组学分析表明，所建立的类器官能有效识别并保留匹配原始组织的肿瘤特征。作为精准医疗的概念验证，我们将构建的类器官与临床治疗同步进行多西他赛和恩杂鲁胺等抗癌药物测试。值得注意的是，体外药物筛选结果与患者临床疗效呈现显著正相关。 结论：综上所述，本研究建立的晚期前列腺癌类器官模型能以经济高效的方式，在一个月内准确预测患者疗效，为临床治疗决策提供可靠依据。
肿瘤(癌症)患者之家