Yeh Yung-Sung, Tsai Hsiang-Lin, Chen Po-Jung, Chen Yen-Cheng, Su Wei-Chih, Chang Tsung-Kun, Huang Ching-Wen, Wang Jaw-Yuan
Division of Trauma and Surgical Critical Care, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Emergency Medicine, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Expert Rev Mol Diagn. 2023 Mar;23(3):231-241. doi: 10.1080/14737159.2023.2188195. Epub 2023 Mar 13.
Colorectal cancer (CRC) is a leading cause of death. For three decades, chemotherapy with or without targeted therapy (provided before or after tumor resection surgery) has been the standard treatment for patients with CRC. Biomarkers are key tools for performing early detection, prognostication, and survival and treatment response predictions. Notably, immune checkpoint inhibitors (ICIs) have transformed prognoses for solid tumors (including CRC).
Although immunotherapy has developed considerably, it is only effective for a small number of microsatellite instability-high (MSIH) cancer cases; such cases represent only 5% of metastatic CRC (mCRC) cases, which are characterized by an immune-inflamed microenvironment that can be rewired against cancer cells through ICI administration. Immunotherapy research is gradually uncovering the mechanism underlying immune resistance in patients with CRC and discovering new biomarkers. For example, studies have clinically validated the associations of deficient mismatch repair system/microsatellite instability, tumor mutation burden, programmed death ligand 1 expression, and polymerase epsilon with CRC in patients undergoing immunotherapy.
Clinical trials documenting the effect of immune checkpoints were performed to produce long-lasting effects for patients with mCRC. Consequently, therapeutic decision-making models are further refined by the inclusion of powerful molecular biomarkers in patients with CRC.
结直肠癌（CRC）是主要的死亡原因之一。三十年来，无论是否联合靶向治疗（在肿瘤切除手术之前或之后进行）的化疗一直是CRC患者的标准治疗方法。生物标志物是进行早期检测、预后评估以及生存和治疗反应预测的关键工具。值得注意的是，免疫检查点抑制剂（ICIs）已经改变了实体瘤（包括CRC）的预后。
尽管免疫疗法已经有了很大发展，但它仅对少数微卫星高度不稳定（MSIH）癌症病例有效；此类病例仅占转移性CRC（mCRC）病例的5%，其特征是具有免疫炎症微环境，可通过给予ICI来对抗癌细胞。免疫疗法研究正在逐步揭示CRC患者免疫抵抗的潜在机制，并发现新的生物标志物。例如，研究已在接受免疫疗法的患者中临床验证了错配修复系统缺陷/微卫星不稳定、肿瘤突变负荷、程序性死亡配体1表达以及聚合酶ε与CRC的关联。
记录免疫检查点作用的临床试验旨在为mCRC患者产生持久疗效。因此，通过纳入CRC患者中强大的分子生物标志物，治疗决策模型得到了进一步完善。
