研究动态
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基于患者的子宫颈癌器官样本的临床前研究,以实现精准医疗。

Preclinical investigation of patient-derived cervical cancer organoids for precision medicine.

发表日期:2022 Dec 30
作者: Hyang Sook Seol, Ju Hee Oh, Eunhye Choi, SangMin Kim, Hyunki Kim, Eun Ji Nam
来源: Journal of Gynecologic Oncology

摘要:

晚期子宫颈癌治疗仍然困难,若出现复发的情况,建议使用个性化治疗而非统一治疗,因为每个人的复发类型都不同。因此,本研究旨在建立一个来自患者的器官样品(PDO)平台,确定化疗、放疗和靶向治疗对子宫颈癌的影响。我们从四名患有不同类型子宫颈癌的患者中建立了器官样品。比较了这些器官样品模型的组织病理学和基因分析,以确定其特征和患者表型的保持情况。每种类型的器官样品也经过了抗癌药物筛选和放射治疗来评估其敏感性。我们建立了来自患者原始肿瘤的主要要素的PDO,包括DNA拷贝数和突变谱。我们使用了美国食品药品监督管理局批准的药库筛选出171种抗癌药物中的7种能对子宫颈癌器官样品产生生长抑制作用的药物。而腺癌和大细胞神经内分泌癌对放疗具有抵抗力,而鳞状细胞癌和绒毛状腺癌对放疗显示出显著反应。我们的研究结果表明,来自患者的子宫颈癌器官样品可用作药物和放疗敏感性测试的平台。这些发现表明,来自患者的子宫颈癌器官样品可以作为个性化医学平台,并为不同类型子宫颈癌患者提供最佳治疗选择。©2023年,亚洲妇科肿瘤学会、韩国妇科肿瘤学会和日本妇科肿瘤学会。
Advanced cervical cancer is still difficult to treat and in the case of recurrent cancer, it is desirable to utilize personalized treatment rather than uniform treatment because the type of recurrence is different for each individual. Therefore, this study aimed to establish a patient-derived organoid (PDO) platform to determine the effects of chemotherapy, radiation therapy, and targeted therapy in cervical cancer.We established organoids from 4 patients with various types of cervical cancer. The histopathological and gene profiles of these organoid models were compared to determine their characteristics and the maintenance of the patient phenotype. Each type of organoid was also subjected to anticancer drug screening and radiation therapy to evaluate its sensitivity.We established PDOs to recapitulate the main elements of the original patient tumors, including the DNA copy number and mutational profile. We selected 7 drugs that showed growth inhibition in cervical cancer organoids out of 171 using an Food and Drug Administration-approved drug library. Moreover, adenocarcinoma and large-cell neuroendocrine carcinoma showed resistance to radiation therapy. whereas squamous cell carcinoma and villoglandular carcinoma showed a significant response to radiotherapy.Our results showed that patient-derived cervical cancer organoids can be used as a platform for drug and radiation sensitivity testing. These findings suggest that patient-derived cervical cancer organoids could be used as a personalized medicine platform and may provide the best treatment options for patients with various subtypes of cervical cancer.© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.