Research Topic

Development of in vitro toxicology methods using organoid systems and toxicogenomic approaches

About this Research Topic

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. 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


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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. 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


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

About Frontiers Research Topics

With their unique mixes of varied contributions from Original Research to Review Articles, Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author.

Topic Editors

Loading..

Submission Deadlines

24 September 2020 Abstract
01 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

Loading..

Topic Editors

Loading..

Submission Deadlines

24 September 2020 Abstract
01 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

Loading..
Loading..

total views article views article downloads topic views

}
 
Top countries
Top referring sites
Loading..