Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients
Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients
复制标题
DOI：
10.1126/scitranslmed.aay2574
复制
发表时间：
2019-10-09
影响因子：
17.1
通讯作者：
Voest, Emile E.
中科院分区：
文献类型：
--
作者：
Ooft, Salo N.;Weeber, Fleur;Voest, Emile E.
对生物标志物预测对癌症化疗的反应性存在明确且未满足的临床需求。我们开发了一种基于转移性病变的患者源性肿瘤类器官（PDO）的体外测试，以识别结直肠癌（CRC）标准治疗化疗的无应答者。在一项前瞻性临床研究中，我们展示了生成和测试PDO用于评价化疗敏感性的可行性。我们的PDO试验预测了80%以上接受伊立替康治疗的患者活检病变的反应，而没有对本可从治疗中获益的患者进行错误分类。然而，这种相关性是基于伊立替康的化疗所特有的，PDO未能预测5-氟尿嘧啶联合奥沙利铂治疗的结果。我们的数据表明，PDO可用于预防癌症患者接受无效的伊立替康为基础的化疗。
There is a clear and unmet clinical need for biomarkers to predict responsiveness to chemotherapy for cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions to identify nonresponders to standard-of-care chemotherapy in colorectal cancer (CRC). In a prospective clinical study, we show the feasibility of generating and testing PDOs for evaluation of sensitivity to chemotherapy. Our PDO test predicted response of the biopsied lesion in more than 80% of patients treated with irinotecan-based therapies without misclassifying patients who would have benefited from treatment. This correlation was specific to irinotecan-based chemotherapy, however, and the PDOs failed to predict outcome for treatment with 5-fluorouracil plus oxaliplatin. Our data suggest that PDOs could be used to prevent cancer patients from undergoing ineffective irinotecan-based chemotherapy.