Patient-derived cell line, xenograft and organoid models in lung cancer therapy

Abstract

Lung cancer accounts for most cancer-related deaths worldwide and has an overall 5-year survival rate of ~15%. Cell lines have played important roles in the study of cancer biology and potential therapeutic targets, as well as pre-clinical testing of novel drugs. However, most experimental therapies that have cleared preclinical testing using established cell lines have failed phase III clinical trials. This suggests that such models may not adequately recapitulate patient tumor biology and clinical outcome predictions.Here, we discuss and compare different pre-clinical lung cancer models, including established cell lines, patient-derived cell lines, xenografts and organoids, summarize the methodology for generating these models, and review their relative advantages and limitations in different oncologic research applications. We further discuss additional gaps in patient-derived pre-clinical models to better recapitulate tumor biology and improve their clinical predictive power.

Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids

“…In contrast to monolayer cultures, 3D organoids can recapitulate the native histoarchitecture by forming an aggregation of different cell types that allows researchers to investigate the pathology mechanisms in the context of tissue organization microenvironment complexity [ 17 ]. Indeed, the applications of iPSC-derived organoids have been extended to basic biological research, medical research, and organ regeneration, such as iPSC-derived lung, brain, vascular, kidney, and retinal organoids [ 18 , 19 , 20 , 21 , 22 ]. Furthermore, human iPSC-derived retinal organoids have been utilized to model human-specific retinal development, disease progression, and drug testing [ 23 ].…”

Hydrogels to engineer tumor microenvironmentsin vitro

“…Review not by engineering mutations into stem cells, but directly from resected patient-derived tumor tissues or biopsies. To date, an immense collection of patient-derived tumor organoids for long-term cultures have been generated and biobanked, including cancers of the lung, 47 breast, 48 gastrointestinal tissues, 49 and pancreas. 50 As these tumor organoid models reflect the molecular profile and inherent heterogeneity in cancer cells found in the corresponding patient, 48 these organoids present tremendous opportunities for drug development and personalized drug testing.…”

From Laboratory Studies to Clinical Trials: Temozolomide Use in IDH-Mutant Gliomas

“…However, further evidence suggests that cell lines are poor representatives of the primary tumor isolated from patients in genetics, mRNA profiles, and protein expression [ 198 ]. Most experimental therapies with promising preclinical results using established cell lines have failed phase III clinical trials [ 199 ]. The development and propagation of mouse models and PDXs are more clinically representative but are time-consuming and costly [ 200 ].…”