About this Research Topic

Background

Organoids are composed of variously differentiated cell types representing an organ/tissue and considered to be cultured similarly to those same organs in vivo. One of the most important advantages of organoids in their utilization for basic and translational research is that they can be established not only from carcinomas but also normal organs and tissues and can be cultured and maintained at least for several months. This advanced approach enables researchers to use organoid-based in vitro models to conduct toxicologic evaluations for risk assessment of environmental factors and carcinogenesis studies in which multi-step processes should be analyzed from normal to cancerous conditions. Recently, organoid-based carcinogenesis models induced by in vitro chemical treatment have been developed. In this model, maximal tolerated doses of genotoxic chemicals were tested in vitro and their tumorigenicity or morphological changes demonstrating malignant transformation, as well as the activation of oncogenic kinases were confirmed after injection to nude mice. These models are applied to detect early molecular events, including genetic and epigenetic changes by various types of carcinogens. In addition, whole-genome-sequencing (WGS) analyses of large numbers of human cancers have revealed mutational signatures, which promise to disclose the diversity of mutational processes underlying the development and etiology of cancers. A compendium of mutational signatures of environmental agents, including not only chemicals but also radiation and reactive oxygens species, was introduced using human-induced pluripotent stem cells (iPSCs) in 2019. These data sets were recognized as a reference of mutation patterns occurring in primitive human iPSCs.
From now on, such toxicogenomic approaches using organoids with variously differentiated cell types should be essential for bridging between experimental data and human cancers. In recent international toxicology conferences, presentations on organoid-based studies for molecular mechanisms of drug toxicities using multi-omics approaches are also increasing. Organoid systems can be established from animals/human tissues, and human iPSCs. In general, human tissue-derived or human iPSCs-derived organoids are considered advantageous for evaluation of drug toxicities and risks of environmental agents. However, it is necessary to consider individual variations in the use of human-originated organoids. On the other hand, not only mouse tissue-derived organoids but also organoids from other animal species are recently cultured and promised to be utilized for evaluation of species differences in chemical/drug reactions.

The aim of this Research Topic is to highlight novel approaches for the elucidation of the mode-of-action of toxicologic effects of drugs and environmental factors for human health via the collaboration between organoid-based technologies and toxicogenomics.
This research topic welcomes articles related to the following areas:

· Use of organoid-based in vitro models to conduct toxicologic and carcinogenic evaluations for risk assessment of environmental agents
· Novel approaches for the elucidation of the mode-of-action of toxicologic effects of drugs and environmental factors
· Use of toxicogenomics approaches to evaluate individual variations in the use of human-originated organoids
· Toxicogenomics approaches using organoids with variously differentiated cell types to bridge between experimental data and human cancers.
· Use of organoids for evaluation of metabolism of drugs and environmental agents
· Preclinical disease models using organoids for drug discovery

Keywords: toxicogenomics, organoids, cell-based, in vitro, cancer models, cell models, organotypic, toxicity, drug development

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