Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Faculty of Health Science, Nord University, Campus Levanger, Norway.
Biomed Pharmacother. 2022 May;149:112923. doi: 10.1016/j.biopha.2022.112923. Epub 2022 Apr 6.
To date, immune checkpoint blockade (ICB) immunotherapy has become one of promise strategies in the management of patients with unresectable or metastatic colorectal cancer (CRC). However, clinical observations showed that not all the patients responded equally to ICBs, certain group of CRC patients with microsatellite-instability-low (MSI-L) phenotype was not sensitive to ICB immunotherapy. In addition, some primary responders might lose their sensitivity and become resistant to ICBs overtime. To obtain a better response rate and therapeutic efficacy, considerable attempts have been made toward to a precision medicine algorithm. Studies showed that multiple strategies based on the patient's individual condition might improve the response and therapeutic efficacy to ICBs. Therefore, we focused on and discussed precision strategies and perspectives e.g., how to early define candidates who will benefit from ICB immunotherapy prior treatment, overcome the primary and acquired resistance and improve the therapeutic response to ICBs in CRC patients with different microsatellite-instability statuses within the context of precision medicine algorithm in this review.
迄今为止，免疫检查点阻断（ICB）免疫疗法已成为不可切除或转移性结直肠癌（CRC）患者治疗的一种有希望的策略。然而，临床观察表明，并非所有患者对 ICB 均有同等反应，某些具有低微卫星不稳定性（MSI-L）表型的 CRC 患者对 ICB 免疫治疗不敏感。此外，一些原发性应答者可能会随着时间的推移失去敏感性并对 ICB 产生耐药性。为了获得更好的反应率和治疗效果，已经尝试了相当多的精准医学算法。研究表明，基于患者个体情况的多种策略可能会提高对 ICB 的反应和治疗效果。因此，我们专注于并讨论了精准策略和观点，例如，如何在精准医学算法的背景下，在治疗前早期确定将从 ICB 免疫治疗中受益的候选者，克服原发性和获得性耐药性，并提高不同微卫星不稳定性状态的 CRC 患者对 ICB 的治疗反应。
