Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Halsted 608, Baltimore, MD, 21287, USA.
Second Department of Propedeutic Surgery, "Laiko" General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
J Gastrointest Surg. 2018 Jul;22(7):1286-1296. doi: 10.1007/s11605-018-3766-1. Epub 2018 Apr 11.
Colorectal liver metastases (CRLM) present an important clinical challenge in both surgical and medical oncology. Despite improvements in management, survival among patients undergoing resection of CRLM is still very variable and there is a paucity of clinical trial data and reliable biomarkers that could guide prognostic forecasts, treatment selection, and follow-up. Fortunately, recent advances in molecular biology and tumor sequencing have identified a number of critical genetic loci and proliferation markers that may hold the key to understanding the biologic behavior of CRLM; specifically, mutations of KRAS, BRAF, TP53, PIK3CA, APC, expression of Ki-67, and the presence of microsatellite instability appear to have a decisive impact on prognosis and response to treatment in patients with CRLM. While the applicability of genetic biomarkers in everyday clinical practice remains conditional on the development of inexpensive bedside sequencing, targeted therapies, and the conduct of appropriate clinical trials, the promise of personalized treatment may be closer to realization than ever before.
结直肠癌肝转移(CRLM)在外科和肿瘤内科均是极具挑战性的临床问题。尽管治疗手段有所改善,但接受 CRLM 切除术患者的生存情况仍然存在很大差异,且临床研究数据和可靠的生物标志物匮乏,无法指导预后预测、治疗选择和随访。幸运的是,分子生物学和肿瘤测序的最新进展已经确定了一些关键的遗传基因座和增殖标志物,这些可能是理解 CRLM 生物学行为的关键;具体而言,KRAS、BRAF、TP53、PIK3CA、APC 的突变、Ki-67 的表达以及微卫星不稳定性的存在似乎对 CRLM 患者的预后和治疗反应具有决定性影响。虽然遗传生物标志物在日常临床实践中的适用性取决于廉价的床边测序、靶向治疗和适当临床试验的开展,但个体化治疗的前景可能比以往任何时候都更加接近现实。