Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China.
Biomed Pharmacother. 2024 Oct;179:117363. doi: 10.1016/j.biopha.2024.117363. Epub 2024 Sep 4.
HER2 amplification is one of the mechanisms that induce drug resistance to anti-EGFR therapy in colorectal cancer. In recent years, data from several randomized clinical trials show that anti-HER2 therapies improved the prognosis of patients with HER2-positive colorectal cancer. These results indicate that HER2 is a promising therapeutic target in advanced colorectal cancer. Despite the anti-HER2 therapies including monoclonal antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates improving the outcomes, less than 30 % of the patients achieve objective response and eventually have drug resistance. It is necessary to explore the primary and secondary mechanisms for the resistance to anti-HER2 therapies, which will pave the way to overcome the drug resistance. Several studies have reported the potential mechanisms for the resistance to anti-HER2 therapies. In this review, we present a comprehensive overview of the recent advances in clinical research, mechanisms of treatment resistance, and strategies for reversing resistance in HER2-positive colorectal cancer patients.
HER2 扩增是诱导结直肠癌患者对抗 EGFR 治疗产生耐药性的机制之一。近年来，几项随机临床试验的数据表明，抗 HER2 治疗改善了 HER2 阳性结直肠癌患者的预后。这些结果表明，HER2 是晚期结直肠癌有前途的治疗靶点。尽管包括单克隆抗体、酪氨酸激酶抑制剂和抗体药物偶联物在内的抗 HER2 治疗改善了疗效，但只有不到 30%的患者获得了客观缓解，最终产生了耐药性。有必要探索抗 HER2 治疗耐药的原发性和继发性机制，这将为克服耐药性铺平道路。有几项研究报告了抗 HER2 治疗耐药的潜在机制。在这篇综述中，我们全面介绍了 HER2 阳性结直肠癌患者在临床研究、治疗耐药机制以及逆转耐药策略方面的最新进展。
