微卫星稳定转移性结直肠癌中免疫检查点抑制剂的现状与潜在挑战
Current Landscape and Potential Challenges of Immune Checkpoint Inhibitors in Microsatellite Stable Metastatic Colorectal Carcinoma.
作者信息
San-Román-Gil María, Torres-Jiménez Javier, Pozas Javier, Esteban-Villarrubia Jorge, Albarrán-Fernández Víctor, Álvarez-Ballesteros Pablo, Chamorro-Pérez Jesús, Rosero-Rodríguez Diana, Orejana-Martín Inmaculada, Martínez-Delfrade Íñigo, Reguera-Puertas Pablo, Fuentes-Mateos Raquel, Ferreiro-Monteagudo Reyes
机构信息
Medical Oncology Department, Ramón y Cajal University Hospital, 28034 Madrid, Spain.
Medical Oncology Department, Clínico San Carlos University Hospital, 28040 Madrid, Spain.
出版信息
Cancers (Basel). 2023 Jan 30;15(3):863. doi: 10.3390/cancers15030863.
Colorectal cancer (CRC) is the third most frequent cancer and the second most common cause of cancer-related death in Europe. High microsatellite instability (MSI-H) due to a deficient DNA mismatch repair (dMMR) system can be found in 5% of metastatic CRC (mCRC) and has been established as a biomarker of response to immunotherapy in these tumors. Therefore, immune checkpoint inhibitors (ICIs) in mCRC with these characteristics were evaluated with results showing remarkable response rates and durations of response. The majority of mCRC cases have high levels of DNA mismatch repair proteins (pMMR) with consequent microsatellite stability or low instability (MSS or MSI-low), associated with an inherent resistance to ICIs. This review aims to provide a comprehensive analysis of the possible approaches to overcome the mechanisms of resistance and evaluates potential biomarkers to establish the role of ICIs in pMMR/MSS/MSI-L (MSS) mCRC.
结直肠癌（CRC）是欧洲第三常见的癌症，也是癌症相关死亡的第二大常见原因。5%的转移性结直肠癌（mCRC）中可发现由于DNA错配修复缺陷（dMMR）系统导致的高微卫星不稳定性（MSI-H），并且已被确立为这些肿瘤中免疫治疗反应的生物标志物。因此，对具有这些特征的mCRC中的免疫检查点抑制剂（ICI）进行了评估，结果显示出显著的反应率和反应持续时间。大多数mCRC病例具有高水平的DNA错配修复蛋白（pMMR），从而导致微卫星稳定或低不稳定性（MSS或MSI-low），与对ICI的固有抗性相关。本综述旨在对克服耐药机制的可能方法进行全面分析，并评估潜在的生物标志物，以确定ICI在pMMR/MSS/MSI-L（MSS）mCRC中的作用。
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