免疫联合靶向治疗在MSS/pMMR型晚期结直肠癌中的研究进展OA
Research Progress of Immunotherapy Combined with Targeted Therapy in MSS/pMMR Advanced Colorectal Cancer
结直肠癌(CRC)是常见的恶性肿瘤,晚期患者的治疗面临严峻挑战.在转移性结直肠癌(mCRC)中,占绝大多数的微卫星稳定(MSS)/错配修复功能完整(pMMR)型患者对单药免疫治疗高度不敏感.近年来,随着对MSS/pMMR型CRC肿瘤免疫微环境机制的深入研究,免疫联合靶向治疗已成为突破其治疗瓶颈的关键方向,包括免疫联合抗血管生成药物、表皮生长因子受体(EGFR)抑制剂、组蛋白去乙酰化酶(HDAC)抑制剂以及MAPK通路抑制剂等组合.尽管当前相关证据仍以早期临床研究为主,但已有多项研究表明免疫联合靶向治疗可以为MSS/pMMR型mCRC患者带来客观缓解率(ORR)的提升及生存获益,且在特定人群中展现出了显著的疗效优势.本文系统综述了相关联合治疗策略的生物学基础及临床研究进展,同时探讨了潜在的获益患者亚群,并对未来的研究方向进行展望,旨在为优化该类患者的个体化治疗模式提供理论依据与临床参考.
Colorectal cancer(CRC)is a common malignant tumor.The treatment of patients with advanced disease still faces severe challenges.Among patients with metastatic colorectal cancer(mCRC),most of those with microsatellite stable(MSS)/proficient mismatch repair(pMMR)tumors are highly insensitive to monotherapy with immune checkpoint inhibitors.With in-depth investigations into the mechanisms of the tumor immune microenvironment in MSS/pMMR CRC,the combination strategies of immunotherapy and targeted therapy have become a key direction to break through the treatment bottleneck in this population.These strategies include combinations of immunotherapy with antiangiogenic agents,epidermal growth factor receptor inhibitors,histone deacetylase inhibitors,and MAPK pathway inhibitors.Although the current relevant evidence is mainly derived from early-phase clinical trials,a number of studies demonstrated that immunotherapy combined with targeted therapy can improve the objective response rate and survival benefit in patients with MSS/pMMR mCRC and shows remarkable efficacy advantages in specific subgroups.This article systematically reviews the biological basis and clinical research progress of relevant combination therapeutic strategies,discusses potential beneficiary subgroups,and prospects future research directions.It aims to provide theoretical evidence and clinical references for optimizing the individualized treatment paradigm for this large patient population.
黄金龙;路平;梁新军;魏少忠
430079 武汉,华中科技大学同济医学院附属湖北肿瘤医院胃肠肿瘤外科||430079 武汉,湖北省结直肠癌临床医学研究中心||430079 武汉,武汉市结直肠癌临床医学研究中心430079 武汉,湖北省结直肠癌临床医学研究中心||430079 武汉,武汉市结直肠癌临床医学研究中心||430079 武汉,华中科技大学同济医学院附属湖北肿瘤医院腹部肿瘤内科430079 武汉,湖北省结直肠癌临床医学研究中心||430079 武汉,武汉市结直肠癌临床医学研究中心||430079 武汉,华中科技大学同济医学院附属湖北肿瘤医院腹部肿瘤内科430079 武汉,华中科技大学同济医学院附属湖北肿瘤医院胃肠肿瘤外科||430079 武汉,湖北省结直肠癌临床医学研究中心||430079 武汉,武汉市结直肠癌临床医学研究中心
医药卫生
结直肠癌免疫治疗靶向治疗微卫星稳定错配修复功能完整
Colorectal cancerImmuno-therapyTargeted therapyMicrosatell-ite stableProficient mismatch repair
《肿瘤防治研究》 2026 (6)
492-498,7
湖北省自然科学基金创新发展联合基金项目(2026AFC1224)湖北省卫健委重点支撑项目(WJ-2023Z011)湖北省肿瘤医院护航人才项目(2025HBC-HHHRC003)湖北省肿瘤医院院内科研项目(2024HBC-HYN13,2025HBCHYN03) Project of Joint Fund for Innovation and Development of Natural Science Foundation of Hubei Province of China(No.2026AFC1224)Health Commission of Hubei Province Scien-tific Research Project(No.WJ2023-Z011)Talent Project of Hubei Cancer Hospital(No.2025HBCHHHRC003)Scientific Research Projects of Hubei Cancer Hospital(No.2024HBCHYN13,2025HBCHYN03)
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