Department of Medical Oncology, Guys and St Thomas' NHS Foundation Trust, Guy's Hospital, Great Maze Pond, SE1 9RT, London, UK.
Recent Pat Anticancer Drug Discov. 2010 Jun;5(2):142-51. doi: 10.2174/157489210790936270.
Targeting the epidermal growth factor receptor (EGFR), an important component in carcinogenesis, is an attractive therapeutic option for selective anticancer therapy. Several EGFR inhibitors, mostly monoclonal antibodies and tyrosine kinase inhibitors are under investigation in the treatment of colorectal cancer. Although there has been some progress in the treatment of colorectal cancer with combination chemotherapy, the repertoire of active agents is still limited. More recently the anti-EGFR drugs cetuximab and panitumumab have made an impact in the treatment of metastatic disease but with variable response rates. Although the appearance of a skin rash confers a higher response rate, immunohistochemical staining of EGFR at baseline does not. Several studies have now focused on identifying predictive biological markers at a molecular level. Exciting data has demonstrated KRAS mutation status to be the first predictive marker of response to anti-EGFR monoclonal antibodies (mAbs) and has led a new era in the development of targeted therapies in colorectal malignant disease. The aim of this review is to evaluate the impact of anti-EGFR therapies in the treatment of metastatic colorectal cancer; and to present the current data on predictive markers including KRAS status, PTEN expression and germinal gene polymorphisms. The relevant patents are discussed.
针对表皮生长因子受体（EGFR），致癌过程中的一个重要组成部分，是一种有吸引力的治疗选择，用于选择性抗癌治疗。几种 EGFR 抑制剂，主要是单克隆抗体和酪氨酸激酶抑制剂，正在研究用于结直肠癌的治疗。尽管联合化疗在结直肠癌治疗方面取得了一些进展，但有效的药物种类仍然有限。最近，抗 EGFR 药物西妥昔单抗和帕尼单抗在转移性疾病的治疗中产生了影响，但反应率不同。虽然皮疹的出现预示着更高的反应率，但 EGFR 的免疫组织化学染色在基线时并不能预测。目前已有多项研究集中在识别分子水平上的预测性生物标志物。令人兴奋的数据表明，KRAS 突变状态是抗 EGFR 单克隆抗体（mAb）反应的第一个预测性标志物，并为结直肠恶性疾病的靶向治疗的发展开辟了一个新时代。本综述旨在评估抗 EGFR 治疗在转移性结直肠癌治疗中的作用，并介绍当前关于预测标志物的研究数据，包括 KRAS 状态、PTEN 表达和生殖基因多态性。讨论了相关专利。
