推动转化医学研究在结直肠免疫肿瘤学领域取得进展。
Advancing translational research for colorectal immuno-oncology.
发表日期:2023 Aug 10
作者:
Elaine M Thomas, Josephine A Wright, Stephen J Blake, Amanda J Page, Daniel L Worthley, Susan L Woods
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
结直肠癌(CRC)是一种常见且致命的疾病。不幸的是,免疫检查点抑制剂(ICIs)在大多数CRC患者中未能引发有效的抗肿瘤反应。最有可能对ICIs产生反应的患者是那些DNA错配修复缺陷(dMMR)和微卫星不稳定(MSI)疾病的患者。然而,对于ICI反应的可靠预测指标尚不足够,即使在dMMR/MSI亚型中也是如此。这与确定增加反应率和预防耐药性的新机制有关,这些目标是持续而至关重要的需求。为了解决早期研究成果转化为有效治疗策略的当前挑战,本综述总结了目前用于指导CRC免疫调节治疗策略开发的临床前测试的现状。重点强调了化学诱导、移植和转基因方法等常用的小鼠模型的局限性和优势。恰当使用现有模型、结合患者衍生数据并开发能够重现人类疾病重要特征的前沿模型,将是加快相关临床相关研究的关键。©2023. 作者(们)。
Colorectal cancer (CRC) is a common and deadly disease. Unfortunately, immune checkpoint inhibitors (ICIs) fail to elicit effective anti-tumour responses in the vast majority of CRC patients. Patients that are most likely to respond are those with DNA mismatch repair deficient (dMMR) and microsatellite instability (MSI) disease. However, reliable predictors of ICI response are lacking, even within the dMMR/MSI subtype. This, together with identification of novel mechanisms to increase response rates and prevent resistance, are ongoing and vitally important unmet needs. To address the current challenges with translation of early research findings into effective therapeutic strategies, this review summarises the present state of preclinical testing used to inform the development of immuno-regulatory treatment strategies for CRC. The shortfalls and advantages of commonly utilised mouse models of CRC, including chemically induced, transplant and transgenic approaches are highlighted. Appropriate use of existing models, incorporation of patient-derived data and development of cutting-edge models that recapitulate important features of human disease will be key to accelerating clinically relevant research in this area.© 2023. The Author(s).