Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Date Issued
2023-04-21
Author(s)
Shie, Ming-You
Fang, Hsin-Yuan
Kan, Kai-Wen
Ho, Chia-Che
Tu, Chih-Yen
Lee, Pei-Chih
Chen, Chia-Hung
Lee, Alvin Kai-Xing
Tien, Ni
Chen, Jian-Xun
Shen, Yu-Cheng
Chang, Jan-Gowth
Shen, Yu-Fang
Lin, Ting-Ju
Wang, Ben
Hung, Mien-Chie
Cho, Der-Yang
Chen, Yi-Wen
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.
Subjects
decellularized extracellular matrix; lung spheroid model; precision medicine; tumor microenvironment
Publisher
WILEY
Type
journal article