Wang G, He Y, Sun Y, Wang W, Qian X, Yu X, Pan Y
Department of Medical Oncology, Anhui, The First Affiliated Hospital of University of Science and Technology of China, No. 17 Lujiang Road, Luyang District, Hefei, 230001, People's Republic of China.
Merck Serono Co. Ltd., Pudong District, Shanghai, People's Republic of China.
Clin Transl Oncol. 2020 Jun;22(6):813-822. doi: 10.1007/s12094-019-02213-9. Epub 2019 Oct 5.
Numerous inherent and acquired genetic alterations have been demonstrated with resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy in metastatic colorectal cancer (mCRC) patients. Although the common oncogenic driver mutations identified include KRAS, NRAS, BRAF, and PI3K, recent studies report a vital role played by human epithelial growth factor receptor-2 (HER2) amplification in acquired resistance to anti-EGFR therapy. HER2 amplification has been associated with poor prognosis in many malignancies including breast and gastric cancer and is also a negative predictor of anti-EGFR therapy. Given the relevance of HER2 amplification in conferring an anti-EGFR resistance, this paper reviews the prevalence of HER2 amplification in mCRC while exploring the prognostic and predictive values of this biomarker. Further, we also discuss the results of the studies that explored the utilization of anti-HER2-targeted therapies in mCRC. HER2-directed therapies have the ability to change the treatment algorithm in clinically relevant small subset of patients with HER2-amplified mCRC.
在转移性结直肠癌（mCRC）患者中，已经证实了许多内在和获得性基因改变与抗表皮生长因子受体（anti-EGFR）治疗耐药有关。虽然已确定的常见致癌驱动基因突变包括KRAS、NRAS、BRAF和PI3K，但最近的研究报告称，人表皮生长因子受体2（HER2）扩增在获得性抗EGFR治疗耐药中发挥着重要作用。HER2扩增与包括乳腺癌和胃癌在内的许多恶性肿瘤的不良预后相关，也是抗EGFR治疗的阴性预测指标。鉴于HER2扩增在赋予抗EGFR耐药性方面的相关性，本文综述了mCRC中HER2扩增的发生率，同时探讨了该生物标志物的预后和预测价值。此外，我们还讨论了探索抗HER2靶向治疗在mCRC中应用的研究结果。HER2导向治疗有能力改变HER2扩增的mCRC临床相关小亚组患者的治疗方案。
