Chakrabarti Sakti, Kasi Anup Kumar, Parikh Aparna R, Mahipal Amit
Department of Hematology-Oncology, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA.
Division of Medical Oncology, University of Kansas, Kansas City, KS 66160, USA.
Cancers (Basel). 2022 Jun 23;14(13):3078. doi: 10.3390/cancers14133078.
Circulating tumor DNA (ctDNA), the tumor-derived cell-free DNA fragments in the bloodstream carrying tumor-specific genetic and epigenetic alterations, represents an emerging novel tool for minimal residual disease (MRD) assessment in patients with resected colorectal cancer (CRC). For many decades, precise risk-stratification following curative-intent colorectal surgery has remained an enduring challenge. The current risk stratification strategy relies on clinicopathologic characteristics of the tumors that lacks precision and results in over-and undertreatment in a significant proportion of patients. Consequently, a biomarker that can reliably identify patients harboring MRD would be of critical importance in refining patient selection for adjuvant therapy. Several prospective cohort studies have provided compelling data suggesting that ctDNA could be a robust biomarker for MRD that outperforms all existing clinicopathologic criteria. Numerous clinical trials are currently underway to validate the ctDNA-guided MRD assessment and adjuvant treatment strategies. Once validated, the ctDNA technology will likely transform the adjuvant therapy paradigm of colorectal cancer, supporting ctDNA-guided treatment escalation and de-escalation. The current article presents a comprehensive overview of the published studies supporting the utility of ctDNA for MRD assessment in patients with CRC. We also discuss ongoing ctDNA-guided adjuvant clinical trials that will likely shape future adjuvant therapy strategies for patients with CRC.
循环肿瘤DNA（ctDNA）是血液中源自肿瘤的游离DNA片段，携带着肿瘤特异性的基因和表观遗传改变，它代表了一种新兴的用于评估接受根治性手术的结直肠癌（CRC）患者微小残留病（MRD）的新工具。几十年来，根治性结直肠癌手术后的精确风险分层一直是一个长期存在的挑战。当前的风险分层策略依赖于肿瘤的临床病理特征，缺乏精确性，导致相当一部分患者接受过度或不足的治疗。因此，一种能够可靠地识别携带MRD的患者的生物标志物对于优化辅助治疗的患者选择至关重要。几项前瞻性队列研究提供了令人信服的数据，表明ctDNA可能是一种强大的MRD生物标志物，优于所有现有的临床病理标准。目前正在进行多项临床试验，以验证基于ctDNA的MRD评估和辅助治疗策略。一旦得到验证，ctDNA技术可能会改变结直肠癌的辅助治疗模式，支持基于ctDNA的治疗升级和降级。本文全面概述了已发表的支持ctDNA用于CRC患者MRD评估的研究。我们还讨论了正在进行的基于ctDNA的辅助临床试验，这些试验可能会塑造未来CRC患者的辅助治疗策略。
