Radiotherapy is a commonly employed treatment for colorectal cancer, yet its radiotoxicity-related impact on healthy tissues raises significant health concerns. This highlights the need to use radioprotective agents to mitigate these side effects. This review presents the current landscape of human translational radiobiology, outlining the limitations of existing models and proposing engineering solutions. We delve into radiotherapy principles, encompassing mechanisms of radiation-induced cell death and its influence on normal and cancerous colorectal cells. Furthermore, we explore the engineering aspects of microphysiological systems to represent radiotherapy-induced gastrointestinal toxicity and how to include the gut microbiota to study its role in treatment failure and success. This review ultimately highlights the main challenges and future pathways in translational research for pelvic radiotherapy-induced toxicity. This is achieved by developing a humanized in vitro model that mimics radiotherapy treatment conditions. An in vitro model should provide in-depth analyses of host-gut microbiota interactions and a deeper understanding of the underlying biological mechanisms of radioprotective food supplements. Additionally, it would be of great value if these models could produce high-throughput data using patient-derived samples to address the lack of human representability to complete clinical trials and improve patients’ quality of life.
放射治疗是结直肠癌的常用治疗手段,但其辐射毒性对健康组织的影响引发了重大健康关切,这凸显了使用辐射防护剂以减轻这些副作用的必要性。本综述阐述了当前人类转化放射生物学的研究现状,指出了现有模型的局限性,并提出了工程学解决方案。我们深入探讨了放射治疗的原理,包括辐射诱导细胞死亡的机制及其对正常与癌变结直肠细胞的影响。此外,我们还研究了微生理系统在模拟放射治疗诱导的胃肠道毒性方面的工程学设计,以及如何纳入肠道微生物群以研究其在治疗成败中的作用。通过开发模拟放射治疗条件的人源化体外模型,本综述最终强调了盆腔放射治疗诱导毒性的转化研究面临的主要挑战与未来路径。理想的体外模型应能深入分析宿主与肠道微生物群的相互作用,并深化对辐射防护性膳食补充剂潜在生物学机制的理解。此外,若这些模型能利用患者来源样本产生高通量数据,将极大弥补临床研究中人类代表性不足的缺陷,从而完善临床试验并提升患者的生活质量。