Lam Rachel C T, Johnson David, Lam Gigi, Li Michelle L Y, Wong Joyce W L, Lam W K Jacky, Chan K C Allen, Ma Brigette
Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir Y. K Pao Centre for Cancer, Hong Kong Cancer Institute, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Oncol. 2022 Sep 29;12:970242. doi: 10.3389/fonc.2022.970242. eCollection 2022.
Advances in Next Generation Sequencing (NGS) technologies have enabled the accurate detection and quantification of circulating tumor-derived (ct)DNA in most gastrointestinal (GI) cancers. The prognostic and predictive utility of ctDNA in patiets with different stages of colorectal (CRC), gastro-esophageal (GEC) and pancreaticobiliary cancers (PBC) are currently under active investigation. The most mature clinical data to date are derived from studies in the prognostic utility of personalized ctDNA-based NGS assays in the detection of minimal residual disease (MRD) and early recurrence after surgery in CRC and other GI cancers. These findings are being validated in several prospective studies which are designed to test if ctDNA could outperform conventional approaches in guiding adjuvant chemotherapy, and in post-operative surveillance in some GI cancers. Several adaptive studies using ctDNA as a screening platform are also being used to identify patients with actionable genomic alterations for clinical trials of targeted therapies. In the palliative setting, ctDNA monitoring during treatment has shown promise in the detection and tracking of clonal variants associated with acquired resistance to targeted therapies and immune-checkpoint inhibitors (ICI). Moreover, ctDNA may help to guide the therapeutic re-challenge of targeted therapies in patients who have prior exposure to such treatment. This review will examine the most updated research findings on ctDNA as a biomarker in CRC, GEC and PBCs. It aims to provide insights into how the unique strengths of this biomarker could be optimally leveraged in improving the management of these GI cancers.
下一代测序（NGS）技术的进步使得在大多数胃肠道（GI）癌症中能够准确检测和定量循环肿瘤来源的（ct）DNA。目前正在积极研究ctDNA在不同阶段的结直肠癌（CRC）、胃食管癌（GEC）和胰胆管癌（PBC）患者中的预后和预测效用。迄今为止，最成熟的临床数据来自于基于个性化ctDNA的NGS检测在CRC和其他GI癌症中检测微小残留病（MRD）和术后早期复发的预后效用研究。这些发现正在多项前瞻性研究中得到验证，这些研究旨在测试ctDNA在指导辅助化疗以及某些GI癌症的术后监测方面是否能优于传统方法。几项将ctDNA用作筛查平台的适应性研究也正在用于识别具有可操作基因组改变的患者，以进行靶向治疗的临床试验。在姑息治疗环境中，治疗期间的ctDNA监测已显示出在检测和追踪与获得性靶向治疗耐药性和免疫检查点抑制剂（ICI）相关的克隆变异方面具有前景。此外，ctDNA可能有助于指导曾接受过此类治疗的患者进行靶向治疗的再次挑战。本综述将审视关于ctDNA作为CRC、GEC和PBC生物标志物的最新研究结果。其目的是深入了解如何最佳利用这种生物标志物的独特优势来改善这些GI癌症的管理。
