Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China,
Cancer Chemother Pharmacol. 2014 Jul;74(1):1-13. doi: 10.1007/s00280-014-2489-6. Epub 2014 Jun 11.
Anti-epidermal growth-factor receptor (EGFR) monoclonal antibody (MoAb) treatment for chemotherapy refractory or metastatic colorectal cancer has obtained great achievement. However, not every colorectal patient responds to such molecular-targeted agent well. Biomarkers associated with anti-EGFR resistance are not limited to KRAS mutation up to now. It was recently reported that cross-talking molecular effectors interacted with EGFR-related pathway were also negative predictor for anti-EGFR treatment. However, the limited data, controversial results, and contradictories between in vitro and clinical studies restrict the clinical application of these new biomarkers. Although the current theory of tumor microenvironment supported the application of multi-target treatment, the results from the clinical studies were less than expected. Moreover, WHO or RECIST guideline for response assessment in anti-EGFR MoAb treatment was also queried by recent AIO KRK-0306 trial. This review focuses on these controversies, contradictories, and limitations, in order to uncover the unmet needs in current status of anti-EGFR MoAb treatment in colorectal cancer.
抗表皮生长因子受体（EGFR）单克隆抗体（MoAb）治疗化疗耐药或转移性结直肠癌已取得重大成就。然而，并非每个结直肠癌患者都对这种分子靶向药物有良好的反应。与抗 EGFR 耐药相关的生物标志物目前不仅限于 KRAS 突变。最近有报道称，与 EGFR 相关途径相互作用的交叉对话分子效应物也是抗 EGFR 治疗的阴性预测因子。然而，有限的数据、相互矛盾的结果以及体外和临床研究之间的矛盾限制了这些新生物标志物的临床应用。尽管肿瘤微环境的当前理论支持多靶点治疗的应用，但临床研究的结果却不尽如人意。此外，最近的 AIO KRK-0306 试验也对 WHO 或 RECIST 指南在抗 EGFR MoAb 治疗中的反应评估提出了质疑。本综述重点讨论了这些争议、矛盾和局限性，以揭示当前结直肠癌抗 EGFR MoAb 治疗中未满足的需求。
