Organoids in recapitulating tumorigenesis driven by risk factors: Current trends and future perspectives

Abstract

Environmental and exogenous/ endogenous factors, in a setting of individual genetic predisposition, contribute to the cancer development. Over the years, epidemical evidence increasingly highlights the correlations of multiple cancer incentives and genetic alterations with cancer incidence. Unraveling the pivotal carcinogenesis events prompted by particular risk factors remarkably advances early surveillance and oncogenesis intervening. Traditional cell-based models and animal-based models are unrealistic and unreliable for translational study, respectively ascribing to the limited tumor heterogeneity and species-related variation. Organoid emerged as a fidelity model that well preserves the properties of its origin. With inherent quality of holistic perspective, organoid is therefore ideally suited for delineating the carcinogenesis under risk exposure, in favor of understanding pathogen-host interactions and alleviating cancer initiation. In this review, we have summarized the organoid model-based evidence that identified or validated carcinogenic risks, mainly including diet, aging, microbial infection, and chemical exposure. In addition, we envisioned the exciting prospect of organoid model in screening promising treatment and/or prevention during tumorigenesis. As a robust 3D in vitro system, organoid has been widespread applied in basial and clinical cancer research, which may elucidate crucial mechanisms of oncogenesis and develop novel targeting strategies.

Possible Strategies to Reduce the Tumorigenic Risk of Reprogrammed Normal and Cancer Cells

“…These organoids need to be characterized by deviating from iPSCs and assembling tissue models using different cell-sourced organoids to merging-on-a-chip technology. These advances are enabling the development of organ-and body-on-a-chip technology, which can be used to mitigate the ethical issues relating to animal use in research [129,173,174]. Recently, Deng's group initiated new trials to decrease the time period and increase the efficiency of chemical reprogramming using human and mouse adipose-derived fibroblasts [4,175].…”

ERCC4: a potential regulatory factor in inflammatory bowel disease and inflammation-associated colorectal cancer

“…Additionally, IECs act as both producers and participants in cytokine and chemokine signaling, which affects the proliferation, migration, and survival of epithelial cells. This creates a favorable local environment for epithelial transformation and tumor development ( 153 – 155 ). The influx of immune cells into the intestinal epithelial layer and lamina propria forms a unique inflammatory microenvironment.…”

Placenta mesenchymal stem cell-derived extracellular vesicles alleviate liver fibrosis by inactivating hepatic stellate cells through a miR-378c/SKP2 axis

“…Therefore, reliable in vitro models are critical for investigating mechanisms and therapeutic targets of hepatic fibrosis. According to recent study findings, organoid culture systems have shown incredible potential to recapitulate the original organ's physiology and pathology in vitro [18][19][20]. While the individual methods may vary, liver organoid models have been applied to the study of hepatocarcinogenesis, screening of anti-fibrosis drugs, and hepato-biliary organogenesis [21,22].…”