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

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.

The preliminary study of patient-derived metastatic brain tumors in a highly mimetic ex vivo spheroid-based physiological model for clinical precision therapeutics

“…Cancer cell-derived organoids and spheroids are considered desirable systems for predicting the response to treatment [4][5][6] . In a prior study conducted by Shie et al 7 , this model was demonstrated to be effective as an ex vivo predictive model for personalized lung cancer therapy, achieving remarkably high accuracy (85%), sensitivity (86.7%), and speci city (80%).…”

“…A response (cell death exceeding 30%) was considered effective. For detailed procedures, refer to the article published by Shie et al 7 Postsurgical management and follow-up…”

Current challenges and practical aspects of molecular pathology for non-small cell lung cancers

“…Preclinical studies (cellular and/or animal models) have shown the efficacy of molecules that may be used for treatment and that are often aimed at currently only hypothetical targets [ 39 , 40 ]. However, no or insufficient clinical data is as yet available concerning the presence and clinical importance of those biomarkers.…”

3D-biofabricated chondrocyte-laden decellularized extracellular matrix-contained gelatin methacrylate auxetic scaffolds under cyclic tensile stimulation for cartilage regeneration

“…The experimental procedures employed in the study were approved by the Animal Experimental Ethics Committee of China Medical University (CMUIACUC-2020-034). The process for preparing decellularized matrix (dECM) using the following previously published protocols with minor modifications [29]. Excess tissue, including tendon and muscle, was removed using sterile surgical equipment, and the cartilage was subjected to decellularization.…”