Hermel David J, Sigal Darren
Department of Medicine, University of Southern California, 2020 Zonal Avenue, Los Angeles, CA 90033, USA.
Division of Hematology/Oncology, Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
J Pers Med. 2019 Jan 16;9(1):5. doi: 10.3390/jpm9010005.
Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit in patients with colorectal cancer has been generally limited to tumors with loss of mismatch repair function and those with specific germline mutations in the DNA polymerase gene. Unfortunately, tumors with these specific mutator phenotypes are in the minority. Recent pre-clinical and clinical studies have begun to reveal encouraging results suggesting that checkpoint inhibitor therapy can be expanded to an increasing number of colorectal tumors with microsatellite stability and the absence of traditional predictive biomarkers of checkpoint inhibitor response. These studies generally rely on combinations of checkpoint inhibitors with chemotherapy, molecular targeted therapy, radiation therapy, or other novel immunomodulatory agents. This article will review the most current data in microsatellite stable colorectal cancer.
检查点抑制剂疗法给当代抗癌治疗带来了一场革命。它使患者的治疗效果有了显著改善,并催生了对新型免疫调节药物和联合疗法的大量研究,改变了癌症治疗的轨迹。然而,结直肠癌患者的临床获益通常仅限于错配修复功能缺失的肿瘤以及DNA聚合酶基因存在特定种系突变的肿瘤。不幸的是,具有这些特定突变表型的肿瘤占少数。最近的临床前和临床研究已开始揭示令人鼓舞的结果,表明检查点抑制剂疗法可扩展至越来越多具有微卫星稳定性且缺乏检查点抑制剂反应传统预测生物标志物的结直肠肿瘤。这些研究通常依赖于检查点抑制剂与化疗、分子靶向治疗、放射治疗或其他新型免疫调节药物的联合使用。本文将综述微卫星稳定型结直肠癌的最新数据。