Patient-derived organoids in human cancer: a platform for fundamental research and precision medicine

Abstract

Cancer is associated with a high degree of heterogeneity, encompassing both inter- and intra-tumor heterogeneity, along with considerable variability in clinical response to common treatments across patients. Conventional models for tumor research, such as in vitro cell cultures and in vivo animal models, demonstrate significant limitations that fall short of satisfying the research requisites. Patient-derived tumor organoids, which recapitulate the structures, specific functions, molecular characteristics, genomics alterations and expression profiles of primary tumors. They have been efficaciously implemented in illness portrayal, mechanism exploration, high-throughput drug screening and assessment, discovery of innovative therapeutic targets and potential compounds, and customized treatment regimen for cancer patients. In contrast to conventional models, tumor organoids offer an intuitive, dependable, and efficient in vitro research model by conserving the phenotypic, genetic diversity, and mutational attributes of the originating tumor. Nevertheless, the organoid technology also confronts the bottlenecks and challenges, such as how to comprehensively reflect intra-tumor heterogeneity, tumor microenvironment, tumor angiogenesis, reduce research costs, and establish standardized construction processes while retaining reliability. This review extensively examines the use of tumor organoid techniques in fundamental research and precision medicine. It emphasizes the importance of patient-derived tumor organoid biobanks for drug development, screening, safety evaluation, and personalized medicine. Additionally, it evaluates the application of organoid technology as an experimental tumor model to better understand the molecular mechanisms of tumor. The intent of this review is to explicate the significance of tumor organoids in cancer research and to present new avenues for the future of tumor research.

Mesothelioma-Associated Fibroblasts Modulate the Response of Mesothelioma Patient-Derived Organoids to Chemotherapy via Interleukin-6

“…PDOs have been shown to recapitulate the cytoarchitecture and, to a significant extent, the heterogeneity of the tumour of origin [12]. Indeed, PDOs can accurately represent the genomic landscape of their source in terms of mutation rates, DNA methylation patterns, gene expression signatures, and copy number variations [13]. This makes PDOs clinically relevant tools for disease modelling towards predictive drug screening [14,15].…”