Division of Molecular Diagnostics, Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan; Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
Cancer Lett. 2014 Feb 1;343(1):1-5. doi: 10.1016/j.canlet.2013.09.012. Epub 2013 Sep 16.
Recent advances in molecular diagnosis and the trend towards personalized medicine have made colorectal cancer one of the tumors where therapies have significantly improved patient survival after metastasis development. KRAS mutations in codon 12 and 13 are recognized biomarkers that are analyzed in clinic previously for anti-EGFR therapies administration. Since originally mutations in both codons were considered as a predictor of lack of response to cetuximab or panitumumab, the European Medicines Agency and the US Food and Drug Administration suggested that patients harboring any of those mutations should be excluded from the treatment. However, subsequent retrospective analysis has shown that mutations in codon 12 and codon 13 of KRAS gene could be different in their biological characteristics and as a result could confer variable effects in patients. In addition and increasing and sometimes contradictory number of solutions have been published demonstrating that patients with mutations in codon 13 could have worse outcome but could obtain a significant clinical benefit from anti-EGFR therapies. Here, we review and update the latest data on the biological role leading to a predictive outcome and benefit from anti-EGFR antibodies in patients with specific KRAS mutations in codon 13.
近年来，分子诊断技术的进步和个体化医学的发展趋势，使得结直肠癌成为治疗方法显著提高转移后患者生存的肿瘤之一。KRAS 基因密码子 12 和 13 中的突变被认为是生物标志物，之前在临床上用于分析抗 EGFR 治疗的应用。由于最初认为这两个密码子的突变都与对西妥昔单抗或帕尼单抗的反应缺乏预测有关，因此欧洲药品管理局和美国食品和药物管理局建议，应将携带这些突变的患者排除在治疗之外。然而，随后的回顾性分析表明，KRAS 基因密码子 12 和 13 中的突变在生物学特征上可能不同，因此可能会对患者产生不同的影响。此外，越来越多的解决方案已经发表，有时甚至相互矛盾，表明密码子 13 中的突变患者可能预后更差，但可以从抗 EGFR 治疗中获得显著的临床获益。在这里，我们回顾和更新了最新的数据，这些数据涉及导致预测结果和特定 KRAS 密码子 13 突变患者从抗 EGFR 抗体中获益的生物学作用。
