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

• Published in: Advanced science Vol. 10; no. 16; pp. e2206603 - n/a
• Main Authors: Shie, Ming‐You, Fang, Hsin‐Yuan, Kan, Kai‐Wen, Ho, Chia‐Che, Tu, Chih‐Yen, Lee, Pei‐Chih, Hsueh, Po‐Ren, 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
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.06.2023; John Wiley and Sons Inc; Wiley
• Subjects: Cancer therapies; Cell culture; Chemotherapy; Collagen; decellularized extracellular matrix; Endothelial Cells - pathology; Fibroblasts; Genomics; Humans; Lung - pathology; Lung cancer; Lung Neoplasms - pathology; lung spheroid model; Medical research; Patients; Physiology; Precision medicine; Rheology; Spheroids; Spheroids, Cellular; Tumor Cells, Cultured; tumor microenvironment; Tumors; decellularized extracellular matrix; precision medicine; tumor microenvironment; lung spheroid model
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202206603

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. A facile route to construct a highly accurate sophisticated ex vivo lung tumor spheroid model for considering patient‐specific therapies. The LdECM provides native‐tissue‐mimetic physicochemical cues that support the organization of spheroids with a hypoxic signature. The developed patient‐derived tumor spheroid model for the prediction of the optimal chemotherapy or target therapy drug for the patient.