患者源性类器官作为结直肠癌精准医疗的临床前平台,Molecular Oncology

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患者源性类器官作为结直肠癌精准医疗的临床前平台
Molecular Oncology ( IF 5.0 ) Pub Date : 2021-11-30 , DOI: 10.1002/1878-0261.13144
Young-Won Cho _{1,

2} , Dong-Wook Min _{1,

2} , Hwang-Phill Kim _{1,

2} , Yohan An ₃ , Sheehyun Kim _{4,

5} , Jeonghwan Youk ₆ , Jaeyoung Chun _{7,

8} , Jong Pil Im ₇ , Sang-Hyun Song ₂ , Young Seok Ju _{3,

6} , Sae-Won Han ₄ , Kyu Joo Park ₉ , Tae-You Kim _{1,

2,

4}

Affiliation

患者来源的类器官被认为是可以通过体外抗癌药物反应评估来帮助指导个性化治疗的模型。然而，试图量化类器官中的体外药物反应并将其与匹配患者的反应进行比较仍然不够充分。在这项研究中，我们调查了类器官的药物反应是否与匹配患者的临床反应和患者的疾病进展相关。从 54 名结直肠癌患者中建立了类器官，这些患者（除了一名患者）之前没有接受任何形式的治疗，并通过全外显子组测序评估肿瘤类器官。用于体外比较在匹配患者的药物反应中，我们根据在类器官中观察到的可变抗癌治疗反应开发了一个“类器官评分”。非常有趣的是，较高的类器官评分与匹配患者的标准护理治疗后较低的肿瘤消退率显着相关。此外，我们证实，与类器官评分较低（<2.5）的患者相比，类器官评分较高（≥ 2.5）的患者无进展生存期较差。此外，为了使用 FDA 批准的药物库评估潜在的药物再利用，将来自疾病进展患者的 10 个肿瘤类器官应用于模拟平台。总之，类器官和类器官评分可以促进抗癌治疗效果的预测，它们可以用作模拟模型，通过药物筛选确定下一个治疗方案。类器官将成为一个有吸引力的平台，可以为结直肠癌患者实施个性化治疗。

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Patient-derived organoids as a preclinical platform for precision medicine in colorectal cancer

Patient-derived organoids are being considered as models that can help guide personalized therapy through in vitro anticancer drug response evaluation. However, attempts to quantify in vitro drug responses in organoids and compare them with responses in matched patients remain inadequate. In this study, we investigated whether drug responses of organoids correlate with clinical responses of matched patients and disease progression of patients. Organoids were established from 54 patients with colorectal cancer who (except for one patient) did not receive any form of therapy before, and tumor organoids were assessed through whole-exome sequencing. For comparisons of in vitro drug responses in matched patients, we developed an ‘organoid score’ based on the variable anticancer treatment responses observed in organoids. Very interestingly, a higher organoid score was significantly correlated with a lower tumor regression rate after the standard-of-care treatment in matched patients. Additionally, we confirmed that patients with a higher organoid score (≥ 2.5) had poorer progression-free survival compared with those with a lower organoid score (< 2.5). Furthermore, to assess potential drug repurposing using an FDA-approved drug library, ten tumor organoids derived from patients with disease progression were applied to a simulation platform. Taken together, organoids and organoid scores can facilitate the prediction of anticancer therapy efficacy, and they can be used as a simulation model to determine the next therapeutic options through drug screening. Organoids will be an attractive platform to enable the implementation of personalized therapy for colorectal cancer patients.

更新日期：2021-11-30

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