Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics

用于临床精准治疗的高度模拟离体肺癌细胞球体生理模型

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作者:Ming-You Shie, Hsin-Yuan Fang, Kai-Wen Kan, Chia-Che Ho, Chih-Yen Tu, Pei-Chih Lee, Po-Ren Hsueh, Chia-Hung Chen, Alvin Kai-Xing Lee, Ni Tien, Jian-Xun Chen, Yu-Cheng Shen, Jan-Gowth Chang, Yu-Fang Shen, Ting-Ju Lin, Ben Wang, Mien-Chie Hung, Der-Yang Cho, Yi-Wen Chen

Abstract

Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient-specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient-derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung-cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co-clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care.

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