Balmaceda Nicole Baranda, Kim Sunnie S
Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Curr Oncol Rep. 2025 Feb;27(2):81-94. doi: 10.1007/s11912-024-01624-4. Epub 2025 Jan 3.
This review addresses the current treatment paradigm and new advancements in the management of microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) esophagogastric cancer (EGC).
While chemotherapy and surgery remain the cornerstone of EGC treatment, MSI-H/dMMR tumors harbor high tumor mutational burden and represent a subset of patients who benefit from immune checkpoint inhibitors (ICI). ICI has been incorporated in the front line setting with and without chemotherapy for advanced disease. Recently, ICI has been studied in the perioperative setting for resectable disease. Though perioperative ICI results in improved response rates, it is not yet clear whether this translates to a survival benefit. Despite high response rates with ICI in this patient population, many do not respond to therapy, representing a major challenge in treatment. Preclinical studies have highlighted potential mechanisms of resistance which will guide drug development and clinical trials.
本综述探讨了微卫星高度不稳定/错配修复缺陷（MSI-H/dMMR）食管胃癌（EGC）治疗的当前模式及新进展。
虽然化疗和手术仍然是EGC治疗的基石，但MSI-H/dMMR肿瘤具有高肿瘤突变负荷，代表了受益于免疫检查点抑制剂（ICI）的患者亚组。ICI已被纳入晚期疾病的一线治疗方案，可联合或不联合化疗。最近，ICI已在可切除疾病的围手术期进行研究。尽管围手术期ICI可提高缓解率，但尚不清楚这是否转化为生存获益。尽管ICI在该患者群体中缓解率较高，但许多患者对治疗无反应，这是治疗中的一个重大挑战。临床前研究突出了潜在的耐药机制，这将指导药物开发和临床试验。
