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患者来源类器官模型预测结直肠癌患者的化疗反应。

Patient-derived Organoid Model for Predicting the Chemoresponse in Patients With Colorectal Cancer.

机构信息

Department of Internal Medicine, Pusan National University College of Medicine, Busan, Republic of Korea.

Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.

出版信息

In Vivo. 2023 Jul-Aug;37(4):1751-1759. doi: 10.21873/invivo.13263.

Abstract

BACKGROUND/AIM: Cancer mortality has decreased due to the contribution of extensive research on cancer treatment, including chemotherapy, radiation, and immunotherapy. However, histopathologically similar tumors originating from the same organ are treated with identical or similar chemotherapeutic regimens regardless of patient characteristics or cancer subtypes. The aim of this study was to evaluate the utility of organoids in predicting responses to chemotherapeutic agents.

PATIENTS AND METHODS

This study retrospectively reviewed patient-derived organoids (PDOs) from 10 colorectal cancer patients to compare chemotherapy responses. Drug sensitivities for 5-fluorouracil (5-FU), cisplatin, oxaliplatin, and irinotecan were compared using GI50 (concentration that inhibits cancer cell growth by 50%).

RESULTS

When organoids were treated with 5-FU, GI50 was the lowest compared to the other three chemotherapeutic agents (cisplatin, oxaliplatin, and irinotecan). The responsiveness to chemotherapeutic agents differed depending on specific patient characteristics including age, tumor location, stage, and gross type. The response of the patients' organoids to chemotherapeutic agents was consistent with the response to chemotherapy actually performed in those patients with cancer recurrence after surgery.

CONCLUSION

PDOs may be useful as a preclinical model in predicting chemotherapy responses in cancer patients.

摘要

背景/目的:由于癌症治疗的广泛研究,包括化疗、放疗和免疫疗法,癌症死亡率已经下降。然而,尽管起源于同一器官的组织病理学相似的肿瘤具有相同或相似的化疗方案,但无论患者特征或癌症亚型如何,都采用相同的化疗方案进行治疗。本研究旨在评估类器官在预测化疗药物反应中的效用。

患者和方法

本研究回顾性分析了 10 名结直肠癌患者的患者来源类器官(PDO),以比较化疗反应。使用 GI50(抑制癌细胞生长 50%的浓度)比较了氟尿嘧啶(5-FU)、顺铂、奥沙利铂和伊立替康的药物敏感性。

结果

当用 5-FU 处理类器官时,GI50 是四种化疗药物(顺铂、奥沙利铂和伊立替康)中最低的。化疗药物的反应取决于特定的患者特征,包括年龄、肿瘤位置、分期和大体类型。患者类器官对化疗药物的反应与手术后癌症复发患者实际进行的化疗反应一致。

结论

PDO 可用作预测癌症患者化疗反应的临床前模型。

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本文引用的文献

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Patient-Derived Organoid Model in the Prediction of Chemotherapeutic Drug Response in Colorectal Cancer.
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Patient-Derived Organoids of Colorectal Cancer: A Useful Tool for Personalized Medicine.
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Application Progress of Organoids in Colorectal Cancer.
Front Cell Dev Biol. 2022 Feb 22;10:815067. doi: 10.3389/fcell.2022.815067. eCollection 2022.
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Patient-derived organoids as a preclinical platform for precision medicine in colorectal cancer.
Mol Oncol. 2022 Jun;16(12):2396-2412. doi: 10.1002/1878-0261.13144. Epub 2022 Jan 1.
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Organoids as a Robust Preclinical Model for Precision Medicine in Colorectal Cancer: A Systematic Review.
Ann Surg Oncol. 2022 Jan;29(1):47-59. doi: 10.1245/s10434-021-10829-x. Epub 2021 Oct 1.
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Patient-Derived In Vitro Models for Drug Discovery in Colorectal Carcinoma.
Cancers (Basel). 2020 May 31;12(6):1423. doi: 10.3390/cancers12061423.
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Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients.
Sci Transl Med. 2019 Oct 9;11(513). doi: 10.1126/scitranslmed.aay2574.

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