Teng Wei, Wu Tai-Chi, Lin Shi-Ming
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
Biomed J. 2024 Nov 17:100815. doi: 10.1016/j.bj.2024.100815.
Hepatocellular carcinoma (HCC) ranks the sixth most common malignancy but the third leading cause of cancer-related mortality in the world. Significant breakthroughs have been made in systemic treatment for HCC over the past two decades, which have improved treatment outcomes. In addition to multiple tyrosine kinase inhibitors (mTKIs), immune checkpoint inhibitors (ICIs) and antiangiogenic drugs are increasingly being applied. The combination of ICI and antiangiogenic or dual ICIs has become the new standard of care due to remarkable response rates. However, currently available systemic regimens are primarily reserved for certain patients in the intermediate and advanced stages who will not benefit from locoregional treatments. Evidence supporting the use of systemic treatment as neoadjuvant or adjuvant therapies in patients with early-stage HCC, especially the high risk of recurrence after curative treatments, remains limited. This review identified recent developments in systemic therapy, including mTKIs and ICIs, considering results on first- and second-line treatment, role of neoadjuvant and adjuvant settings, and combination with loco-regional therapy. Various ongoing clinical trials regarding the role of systemic therapies and potential novel targets in patients with early-, intermediate-, and advanced-stage HCC were also summarized and revealed that systemic therapy is no longer limited to advanced-stage HCC. Moreover, the introduction of T-cell redirecting strategies, including bispecific antibodies and chimeric antigen receptor T cells, has revolutionized the treatment landscape for HCC. Future research should focus on an in-depth exploration of the mechanisms governing the establishment of tumor barriers.
肝细胞癌（HCC）是全球第六大常见恶性肿瘤，但却是癌症相关死亡的第三大主要原因。在过去二十年中，HCC的全身治疗取得了重大突破，改善了治疗效果。除了多种酪氨酸激酶抑制剂（mTKIs）外，免疫检查点抑制剂（ICIs）和抗血管生成药物的应用也越来越广泛。ICI与抗血管生成药物联合或双ICI联合由于显著的缓解率已成为新的标准治疗方案。然而，目前可用的全身治疗方案主要适用于某些中晚期患者，这些患者无法从局部区域治疗中获益。支持将全身治疗作为早期HCC患者新辅助或辅助治疗的证据仍然有限，尤其是在根治性治疗后复发风险较高的患者中。本综述确定了全身治疗的最新进展，包括mTKIs和ICIs，考虑了一线和二线治疗的结果、新辅助和辅助治疗的作用以及与局部区域治疗的联合。还总结了关于全身治疗在早期、中期和晚期HCC患者中的作用以及潜在新靶点的各种正在进行的临床试验，结果显示全身治疗不再局限于晚期HCC。此外，包括双特异性抗体和嵌合抗原受体T细胞在内的T细胞重定向策略的引入彻底改变了HCC的治疗格局。未来的研究应专注于深入探索肿瘤屏障形成机制。
