Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 Xisi Road, 226001 Nantong, Jiangsu, China.
Department of Radiology, Wake Forest School of Medicine, One Medical Center Boulevard, Winston-Salem, 27157 NC, USA.
Int J Biol Sci. 2022 Mar 28;18(7):2729-2743. doi: 10.7150/ijbs.70406. eCollection 2022.
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 system, organoid has been widespread applied in basial and clinical cancer research, which may elucidate crucial mechanisms of oncogenesis and develop novel targeting strategies.
环境和外源性/内源性因素，在个体遗传易感性的背景下，有助于癌症的发展。多年来，流行病学证据越来越多地强调了多种癌症诱因和遗传改变与癌症发病率的相关性。揭示特定危险因素引发的关键致癌事件显著促进了早期监测和肿瘤发生干预。传统的基于细胞的模型和基于动物的模型分别由于肿瘤异质性和物种相关的变异性有限，对于转化研究来说是不现实和不可靠的。类器官作为一种保真度模型，很好地保留了其起源的特性。类器官具有整体视角的固有质量，因此非常适合描绘暴露于风险下的致癌过程，有利于理解病原体-宿主相互作用并减轻癌症的发生。在这篇综述中，我们总结了基于类器官模型的证据，这些证据确定或验证了致癌风险，主要包括饮食、衰老、微生物感染和化学暴露。此外，我们还展望了类器官模型在肿瘤发生过程中筛选有前途的治疗和/或预防方法的令人兴奋的前景。作为一个强大的 3D 系统，类器官已广泛应用于基础和临床癌症研究，这可能阐明肿瘤发生的关键机制并开发新的靶向策略。
