Tran Nguyen H, Cavalcante Ludimila L, Lubner Sam J, Mulkerin Daniel L, LoConte Noelle K, Clipson Linda, Matkowskyj Kristina A, Deming Dustin A
Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, and University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Ther Adv Med Oncol. 2015 Sep;7(5):252-262. doi: 10.1177/1758834015591952. Epub 2015 Jul 5.
When considering treatment options for patients with metastatic colorectal cancer (mCRC), molecular profiling has become a pivotal component in guiding clinical decisions. FOLFOX and FOLFIRI (fluorouracuil, leucovorin plus oxaliplatin or ininotecan, respectively) are the standard base regimens used for the treatment of mCRC. Biologic agents, such as the epidermal growth factor receptor (EGFR) targeted therapies, cetuximab and panitumumab and the vascular endothelial growth factor monoclonal antibody, bevacizumab, are safe and effective in the first-line setting. The most efficacious use of these agents in terms of timing and selection of the right patient population continues to be debated. Here we review multiple investigations into the effectiveness of treatment options as a function of the mutations present in colon cancers. Early studies have reported that mutations at exon 2 predict resistance to EGFR targeted therapies. More recently the data have expanded to include mutations at exons 3 and 4 and mutations at exons 2, 3 and 4 as well as other biomarkers including and , leading to the evolution of the treatment of mCRC to a more precision-based approach. As our understanding of relevant biomarkers increases, and data from both molecular profiling and treatment response become more readily available, treatment options will become more precise and their outcomes more effective.
在考虑转移性结直肠癌(mCRC)患者的治疗方案时,分子谱分析已成为指导临床决策的关键组成部分。FOLFOX和FOLFIRI(分别为氟尿嘧啶、亚叶酸钙加奥沙利铂或伊立替康)是用于治疗mCRC的标准基础方案。生物制剂,如表皮生长因子受体(EGFR)靶向疗法西妥昔单抗和帕尼单抗以及血管内皮生长因子单克隆抗体贝伐单抗,在一线治疗中是安全有效的。这些药物在使用时机和合适患者群体选择方面的最有效应用仍存在争议。在此,我们综述了多项关于结肠癌中存在的突变与治疗方案有效性关系的研究。早期研究报告称,外显子2的突变预示着对EGFR靶向疗法耐药。最近,数据已扩展到包括外显子3和4的突变以及外显子2、3和4的突变,以及其他生物标志物,包括[此处原文缺失具体生物标志物内容]和[此处原文缺失具体生物标志物内容],这使得mCRC的治疗演变为一种更基于精准医学的方法。随着我们对相关生物标志物的理解不断增加,并且分子谱分析和治疗反应的数据更容易获得,治疗方案将变得更加精准,其效果也会更显著。