研究动态
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通过开发一种快速患者源异种移植模型,预测恶性神经胶质肿瘤的化疗药物敏感性/耐受性。

The development of a rapid patient-derive d xenograft model to predict chemotherapeutic drug sensitivity/resistance in malignant glial tumors.

发表日期:2023 Feb 23
作者: Martine Charbonneau, Kelly Harper, Karine Brochu-Gaudreau, Alexis Perreault, Laurent-Olivier Roy, Fabrice Lucien, Shulan Tian, David Fortin, Claire M Dubois
来源: NEURO-ONCOLOGY

摘要:

高级别胶质瘤(HGG)是侵袭性脑肿瘤,患者存活期短,对疗法反应有限,需要开发工具来改善患者预后。患者来源的异种移植(PDX)模型,如小鼠PDX,作为个性化肿瘤学方法的潜在Avatar平台已经出现,但部分人类移植物的成功生长难度和小鼠形成肿瘤所需的长时间使它们不适用于HGG。我们使用快速高效的卵外几胎膜(CAM)培养系统评估HGG患者的肿瘤药物选择的功效。将来自60位患者的新鲜胶质瘤组织片段植入CAM,其中包括难以生长的IDH突变样本,成功建立CAM肿瘤异种移植,就诊于7天内,在肿瘤取样率为98.3%。这些异种移植忠实再现了原发性肿瘤的组织学和分子特征,个体片段形成肿瘤的能力预示了患者预后较差的可能性。对药物敏感或药物耐受性异种移植的治疗表明,CAM胶质瘤检测可以以与患者接受剂量相一致的剂量测试肿瘤对特莫唑酰胺和卡铂的敏感性。在涉及14名HGG患者的概念验证研究中,我们观察到CAM异种移植对特莫唑酰胺或卡铂的反应与患者的临床反应之间的相关性为100%。CAM-glioma模型是一种快速可靠的检测方法,具有作为药物发现的补充模型和实时Avatar平台,以预测HGG患者最佳治疗的潜力。©作者(2023年)由牛津大学出版社代表神经肿瘤学会出版。
High-grade gliomas (HGG) are aggressive brain tumors associated with short median patient survival and limited response to therapies, driving the need to develop tools to improve patient outcomes. Patient-derived xenograft (PDX) models, such as mouse PDX, have emerged as potential Avatar platforms for personalized oncology approaches, but the difficulty for some human grafts to grow successfully and the long time required for mice to develop tumors preclude their use for HGG.We used a rapid and efficient ex-ovo chicken embryo ChorioAllantoic Membrane (CAM) culture system to evaluate the efficacy of oncologic drug options for HGG patients.Implantation of fresh glioma tissue fragments from 59 of 60 patients, that include difficult to growth IDH-mutated samples, successfully established CAM tumor xenografts within 7 days, with a tumor take rate of 98.3%. These xenografts faithfully recapitulate the histological and molecular characteristics of the primary tumor, and the ability of individual fragments to form tumors was predictive of poor patient prognosis. Treatment of drug-sensitive or drug-resistant xenografts indicates that the CAM-glioma assay enables testing tumor sensitivity to temozolomide and carboplatin at doses consistent with those administered to patients. In a proof-of-concept study involving 14 HGG patients, we observed a correlation of 100% between the CAM xenograft response to temozolomide or carboplatin and the clinical response of patients.The CAM-glioma model is a fast and reliable assay that has the potential to serve as a complementary model to drug discovery and a real-time Avatar platform to predict the best treatment for HGG patients.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.