高表达甲胎蛋白的晚期肝细胞癌靶向治疗进展

Advances in Targeted Therapy for Advanced Hepatocellular Carcinoma with High Alpha-Fetoprotein Expression

摘要: 肝细胞癌(HCC)伴血清甲胎蛋白(AFP)高表达(AFP ≥ 400 ng/mL)的患者亚群，代表了一个具有独特生物学特征、高度侵袭性和不良预后的高危群体。该亚群在临床上与更大的肿瘤负荷、更高的血管侵犯率及复发风险密切相关。其病理生理学基础涉及关键致癌信号通路的异常激活、上皮–间质转化(EMT)过程的驱动，以及免疫抑制性肿瘤微环境的形成。近年来，针对这一特定人群的靶向治疗及联合策略已取得重要进展，显著改变了治疗格局。本文旨在系统回顾针对高表达AFP晚期肝细胞癌的靶向治疗及其联合方案的演进与关键证据。未来的研究方向应致力于深入阐明AFP驱动HCC进展的分子机制，推动基于生物标志物的前瞻性临床试验，并整合多组学与人工智能技术，以实现真正意义上的个体化治疗，最终改善这一高危患者群体的生存结局。

Abstract: The patient subgroup with hepatocellular carcinoma (HCC) and high serum alpha-fetoprotein (AFP) levels (AFP ≥ 400 ng/mL) constitutes a distinct, high-risk population characterized by unique biological features, highly aggressive behavior, and a poor prognosis. Clinically, this subgroup is strongly associated with a greater tumor burden, a higher incidence of vascular invasion, and an increased risk of recurrence. The underlying pathophysiology involves the aberrant activation of key oncogenic signaling pathways, the induction of epithelial-mesenchymal transition (EMT), and the establishment of an immunosuppressive tumor microenvironment. In recent years, significant progress in targeted therapies and combination strategies for this specific patient population has substantially altered the therapeutic landscape. This review aims to systematically summarize the evolution of, and key evidence for, targeted therapies and their combination regimens in advanced, AFP-high HCC. Future research should focus on further elucidating the molecular mechanisms by which AFP drives HCC progression, advancing biomarker-driven prospective clinical trials, and integrating multi-omics with artificial intelligence. These efforts are crucial for realizing true personalized therapy and ultimately improving the survival outcomes for this high-risk patient population.