Němeček R, Svoboda M, Slabý O
Klin Onkol. 2016;29(3):187-95. doi: 10.14735/amko2016187.
The combination of modern systemic chemotherapy and anti-EGFR monoclonal antibodies improves overall survival and quality of life for patients with metastatic colorecal cancer. By contrast, the addition of anti-EGFR therapy to the treatment regime of resistant patients may lead to worse progression-free survival and overall survival. Therefore, identifying sensitive and resistant patients prior to targeted therapy of metastatic colorecal cancer is a key point during the initial decision making process. Previous research shows that primary resistance to EGFR blockade is in most cases caused by constitutive activation of signaling pathways downstream of EGFR. Of all relevant factors (mutation of KRAS, NRAS, BRAF, and PIK3CA oncogenes, inactivation of tumor suppressors PTEN and TP53, amplification of EGFR and HER2, and expression of epiregulin and amphiregulin, mikroRNA miR-31-3p, and miR-31-5p), only evaluation of KRAS and NRAS mutations has entered routine clinical practice. The role of the other markers still needs to be validated. The ongoing benefit of anti-EGFR therapy could be indicated by specific clinical parameters measured after the initiation of targeted therapy, including early tumor shrinkage, the deepness of the response, or hypomagnesemia. The accuracy of predictive dia-gnostic tools could be also increased by examining a combination of predictive markers using next generation sequencing methods. However, unjustified investigation of many molecular markers should be resisted as this may complicate interpretation of the results, particularly in terms of their specific clinical relevance.
The aim of this review is to describe current possibilities with respect to predicting responses to EGFR blockade in the context of the EGFR pathway, and the utilization of such results in routine clinical practice.
现代全身化疗与抗表皮生长因子受体（EGFR）单克隆抗体联合使用可提高转移性结直肠癌患者的总生存期和生活质量。相比之下，在耐药患者的治疗方案中添加抗EGFR治疗可能会导致无进展生存期和总生存期更差。因此，在转移性结直肠癌靶向治疗之前识别敏感和耐药患者是初始决策过程中的关键要点。先前的研究表明，在大多数情况下，对EGFR阻断的原发性耐药是由EGFR下游信号通路的组成性激活引起的。在所有相关因素（KRAS、NRAS、BRAF和PIK3CA癌基因突变、肿瘤抑制因子PTEN和TP53失活、EGFR和HER2扩增、表皮调节素和双调蛋白表达、微小RNA miR-31-3p和miR-31-5p）中，只有KRAS和NRAS突变的评估已进入常规临床实践。其他标志物的作用仍需验证。靶向治疗开始后测量的特定临床参数，包括早期肿瘤缩小、反应深度或低镁血症，可表明抗EGFR治疗的持续益处。通过使用下一代测序方法检查预测标志物的组合，也可以提高预测诊断工具的准确性。然而，应避免对许多分子标志物进行不合理的研究，因为这可能会使结果的解释复杂化，特别是在其具体临床相关性方面。
本综述的目的是描述在EGFR通路背景下预测对EGFR阻断反应的当前可能性，以及在常规临床实践中利用这些结果的情况。
