Microsatellite instability (MSI) is a biological condition associated with inflamed tumors, high tumor mutational burden (TMB), and responses to immune checkpoint inhibitors. In colorectal cancer (CRC), MSI tumors are found in 5% of patients in the metastatic setting and 15% in early-stage disease. Following the impressive clinical activity of immune checkpoint inhibitors in the metastatic setting, associated with deep and long-lasting responses, the development of immune checkpoint inhibitors has expanded to early-stage disease. Several phase II trials have demonstrated a high rate of pathological complete responses, with some patients even spared from surgery. However, in both settings, not all patients respond and some responses are short, emphasizing the importance of the ongoing search for accurate biomarkers. While various biomarkers of response have been evaluated in the context of MSI CRC, includingB2MandJAK1/2 mutations, TMB,WNTpathway mutations, and Lynch syndrome, with mixed results, liver metastases have been associated with a lack of activity in such strategies. To improve patient selection and treatment outcomes, further research is required to identify additional biomarkers and refine existing ones. This will allow for the development of personalized treatment approaches and the integration of novel therapeutic strategies for MSI CRC patients with liver metastases.
微卫星不稳定性（MSI）是一种与炎症性肿瘤、高肿瘤突变负荷（TMB）以及对免疫检查点抑制剂反应相关的生物学状态。在结直肠癌（CRC）中，转移性患者中MSI肿瘤的发生率为5%，早期患者中为15%。随着免疫检查点抑制剂在转移性患者中展现出显著的临床活性，并伴随深度且持久的疗效反应，其应用已扩展至早期疾病阶段。多项II期临床试验已证实其可带来较高的病理完全缓解率，部分患者甚至可免于手术。然而，无论在何种疾病阶段，并非所有患者均能产生应答，且部分应答持续时间较短，这凸显了持续探索精准生物标志物的重要性。尽管已在MSI结直肠癌背景下评估了多种疗效相关生物标志物，包括B2M和JAK1/2基因突变、TMB、WNT通路突变以及林奇综合征，但结果参差不齐。值得注意的是，肝转移的存在与这类治疗策略的疗效缺失相关。为优化患者选择并改善治疗结局，需进一步研究以发现新的生物标志物并完善现有标志物体系，从而为伴有肝转移的MSI结直肠癌患者制定个体化治疗方案并整合新型治疗策略。
肿瘤(癌症)患者之家