Colorectal cancer (CRC) remains a significant global health burden. While early-stage CRC has a high survival rate, most patients are diagnosed with advanced disease, necessitating more effective and less toxic therapeutic targets. This review examines recent advancements, challenges, and future directions in targeted therapies for CRC, focusing on HER inhibitors. We assess the efficacy of monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) and explore strategies to overcome resistance mechanisms. Targeted therapies like cetuximab and panitumumab have improved outcomes for CRC patients with wild-type KRAS. However, resistance mechanisms and intra- and inter-tumour heterogeneity limit their effectiveness. Recent advancements include the development of dual TKIs, antibody/drug conjugates (ADCs), bispecific antibodies, and CAR-T cells against HER family members and other targets that are showing promise in preclinical and clinical trials. Targeted therapies have transformed CRC treatment, but more research is needed to overcome some of the current challenges, such as late diagnosis and the heterogenous nature of CRC, as well as the discovery of more reliable biomarkers for response to the therapy and patient selection. Future research should focus on identifying novel biomarkers of diagnostic, prognostic, and predictive value, developing next-generation inhibitors, drug repurposing, and combining small-molecule targeted therapies with immunotherapy. Such advances could ultimately help increase both the treatment options and outcomes for patients with CRC.
结直肠癌（CRC）仍是全球重大健康负担。尽管早期结直肠癌患者生存率较高，但多数患者确诊时已属晚期，亟需更有效且毒性更低的治疗靶点。本综述探讨结直肠癌靶向治疗的最新进展、挑战与未来方向，重点关注HER抑制剂。我们评估单克隆抗体（mAbs）和酪氨酸激酶抑制剂（TKIs）的疗效，并探索克服耐药机制的策略。西妥昔单抗和帕尼单抗等靶向药物已改善KRAS野生型结直肠癌患者的预后，但耐药机制及肿瘤内/间异质性限制了其疗效。最新进展包括针对HER家族及其他靶点的双靶点TKIs、抗体偶联药物（ADCs）、双特异性抗体和CAR-T细胞的研发，这些在临床前及临床试验中展现出潜力。靶向治疗已改变结直肠癌的治疗格局，但仍需更多研究以应对当前挑战，如晚期诊断、肿瘤异质性，以及寻找更可靠的疗效预测生物标志物和患者筛选指标。未来研究应聚焦于发现具有诊断、预后及预测价值的新型生物标志物，开发新一代抑制剂，探索药物再利用，并将小分子靶向治疗与免疫疗法相结合。这些进展有望最终为结直肠癌患者提供更多治疗选择并改善临床结局。
肿瘤(癌症)患者之家