The selection of effective therapeutic agents is critical for improving the survival of patients with renal cell carcinoma (RCC). The aim of the present study was to develop an ex vivo drug testing assay using patient‑derived tumor organoid (TO) cultures. For this purpose, surgical tumor specimens were obtained from 20 patients with RCC. TOs were developed ex vivo from freshly resected RCC tumors, and their histopathological and molecular characteristics were evaluated using histological staining and whole‑exome sequencing (WES). Using a cell viability assay, the therapeutic efficacy of standard of care tyrosine kinase inhibitors in RCC TOs was determined. It was found that TOs recapitulated the histological features of primary RCC tumors. Using WES, a strong concordance was identified at the genetic level between the primary tumors and their corresponding TOs. Using patient‑derived TO models, a prototype of an ex vivo drug testing assay was developed, and it was found that RCC TOs exhibited differential responses to sunitinib, pazopanib, cabozantinib, axitinib and sorafenib treatment. On the whole, although the predictive value of the current assay has to be tested and validated in future clinical studies, the findings of the present study demonstrate a novel approach for ex vivo drug testing in patient‑derived TO models, which may have potential for use in the personalized treatment of cancer patients.

中文翻译：

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患者来源的肿瘤类器官的开发和肾细胞癌的药物测试模型。

选择有效的治疗药物对于提高肾细胞癌 (RCC) 患者的存活率至关重要。本研究的目的是使用源自患者的肿瘤类器官 (TO) 培养物开发一种离体药物测试方法。为此，从 20 名 RCC 患者获得手术肿瘤标本。TO 是在体外开发的来自新鲜切除的 RCC 肿瘤，并使用组织学染色和全外显子组测序 (WES) 评估它们的组织病理学和分子特征。使用细胞活力测定，确定了标准护理酪氨酸激酶抑制剂在 RCC TO 中的治疗功效。发现 TOs 概括了原发性 RCC 肿瘤的组织学特征。使用 WES，在原发肿瘤与其相应的 TO 之间的遗传水平上确定了很强的一致性。使用源自患者的 TO 模型，一个离体的原型开发了药物检测分析，发现 RCC TOs 对舒尼替尼、帕唑帕尼、卡博替尼、阿西替尼和索拉非尼治疗表现出不同的反应。总体而言，虽然当前检测的预测价值必须在未来的临床研究中进行测试和验证，但本研究的结果证明了一种在患者来源的 TO 模型中进行体外药物测试的新方法，这可能有潜力用于癌症患者的个性化治疗。