Division of Medical Oncology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Anticancer Res. 2024 May;44(5):2103-2108. doi: 10.21873/anticanres.17015.
BACKGROUND/AIM: The DNA checkpoint (DNACHK) pathway is engaged in signaling the need for cell cycle arrest. This pathway is being actively researched to assess its role in cancer immunotherapy. PATIENTS AND METHODS: A total of 62 patients participated in this study. These patients were treated with immune checkpoint inhibitors (ICIs) for advanced biliary tract cancers (BTCs) from March 2020 to August 2022 at Samsung Medical Center. DNACHK mutated were defined as genomic alterations, such as single nucleotide variants, multi-nucleotide variants, and short insertion and deletions in seven genes; checkpoint kinase 1 (CHEK1), checkpoint kinase 2 (CHEK2), BRCA1, DNA repair-associated (BRCA1), the serine/threonine kinase ATM, the serine/threonine kinase ATR, mediator of DNA damage checkpoint 1 (MDC1) and tumor protein p53 binding protein 1 (TP53BP1). We analyzed the effect of DNACHK mutations on the efficacy of ICIs in advanced BTCs. RESULTS: Patient median age at diagnosis was 68.0 years. 10 patients (16.1%) had GB cancer; the remaining patients (n=52, 83.9%) were diagnosed with cholangiocarcinoma. Thirty-seven (59.7%) patients were categorized into the DNACHK wild-type (WT) group and 25 (40.3%) into the DNACHK mutated (MT) group. The most observed DNA checkpoint mutations were ATM mutations (n=14). Patients in the DNACHK MT group had better disease control rate (DCR) than patients in the DNACHK WT (60.0% vs. 48.6%, p=0.53). Median overall survival (OS) was 8.1 months (95% CI 5.1-22.8) in the MT group and 5.6 months (95%CI 3.1-11.0) in the WT group (p=0.33). CONCLUSION: The DNACHK pathway is expected to serve as a potential biomarker for ICI treatment.
背景/目的：DNA 检查点（DNACHK）途径参与信号传递，以指示细胞周期停滞的需求。该途径正在被积极研究，以评估其在癌症免疫治疗中的作用。
患者和方法：共有 62 名患者参与了这项研究。这些患者于 2020 年 3 月至 2022 年 8 月在三星医疗中心接受免疫检查点抑制剂（ICIs）治疗晚期胆道癌（BTC）。DNACHK 突变被定义为基因组改变，如单核苷酸变异、多核苷酸变异以及七个基因中的短插入和缺失；检查点激酶 1（CHEK1）、检查点激酶 2（CHEK2）、BRCA1、DNA 修复相关（BRCA1）、丝氨酸/苏氨酸激酶 ATM、丝氨酸/苏氨酸激酶 ATR、DNA 损伤检查点 1 介导因子（MDC1）和肿瘤蛋白 p53 结合蛋白 1（TP53BP1）。我们分析了 DNACHK 突变对晚期 BTC 中 ICIs 疗效的影响。
结果：患者诊断时的中位年龄为 68.0 岁。10 名患者（16.1%）患有胆囊癌；其余患者（n=52，83.9%）被诊断为胆管癌。37 名（59.7%）患者归入 DNACHK 野生型（WT）组，25 名（40.3%）归入 DNACHK 突变型（MT）组。最常见的 DNA 检查点突变是 ATM 突变（n=14）。DNACHK MT 组患者的疾病控制率（DCR）优于 DNACHK WT 组（60.0% vs. 48.6%，p=0.53）。MT 组的中位总生存期（OS）为 8.1 个月（95%CI 5.1-22.8），WT 组为 5.6 个月（95%CI 3.1-11.0）（p=0.33）。
结论：DNACHK 途径有望成为ICI 治疗的潜在生物标志物。
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