基于患者源性口腔鳞状细胞癌类器官的药敏分析与初步临床应用

Drug Sensitivity Analysis and Preliminary Clinical Application Based on Patient-derived Organoid in Oral Squamous Cell Carcinoma.

目的:基于所建立的患者源性口腔鳞状细胞癌类器官模型进行药物敏感性实验,对相应患者制定个性化药物治疗方案,观察其疗效与实验结果的匹配性。方法:本研究将通过活检或根治手术获得新鲜口腔鳞状细胞癌标本建立患者源性类器官模型,依托此模型对6种治疗口腔鳞状细胞癌药物(顺铂、紫杉醇、5-FU、西妥昔单抗、阿培利司、Nutlin-3)的敏感性进行测定,并对其中4例活检患者参考实验结果制定个性化用药方案,观察两个疗程后的近期治疗效果。结果:本研究成功建立了10例OSCC类器官(成功率10/12,83.3%),均可稳定传代、扩增达4代以上,且与亲本肿瘤组织表现出高度一致的组织病理学特征。口腔鳞状细胞癌类器官模型在药敏实验结果中表现出个体化差异,4例接受药物治疗的患者肿瘤控制结果均达到部分缓解标准,与实验结果一致。结论:本实验建立的患者源性口腔鳞状细胞癌类器官模型高度还原了同源亲本肿瘤的组织病理学特点,基于该模型的体外药敏实验与相应患者临床治疗反应一致,为建立个性化口腔鳞状细胞癌精准药物治疗新体系奠定基础。

Objective:To perform drug sensitivity experiments on patient-derived oral squamous cell carcinoma(OSCC)organoid models and to design individualized drug therapies for the corresponding patients.Mehthods:In the present study,patient-derived organoid(PDO)models were established by obtaining fresh specimens through biopsy or radical operation.These models were used to determine the sensitivity of six drugs(cisplatin,paclitaxel,5-FU,Cetuximab,Alpelisib,and Nutlin-3)to OSCC.Four of the biopsy patients were given individualized medication according to the experimental results and the short-term therapeutic effect was observed after two courses of treatment.Results:Ten OSCC organoids were successfully established(success rate=10/12,83.3%),which could be stably passaged and amplified for more than four generations.The histopathology characteristics of OSCC were highly consistent with those of their parental tumor tissues.The PDO models derived from different patients showed individual differences in the results of drug sensitivity tests.The tumor control results of 4 biopsy patients all met the partial remission criteria,which were consistent with the experimental results.Conclusion:The histopathological characteristics of the established OSCC PDO models were highly similar to those of their parental tumors.The results of the in vitro drug sensitivity tests based on these models were consistent with the clinical treatment response of the corresponding patients,laying a foundation for the establishment of a new individualized and precise drug treatment system for OSCC.