Department of Medical Microbiology and Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Gastroenterology, Shanghai Jing'an District Central Hospital, Fudan University, Shanghai 200040, China.
Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188441. doi: 10.1016/j.bbcan.2020.188441. Epub 2020 Sep 30.
A couple of molecular-targeting medications, such as Lenvatinib, are available for the treatment of hepatocellular carcinoma (HCC) in addition to Sorafenib in an advanced stage. Approval for the use of immune check-point inhibitors, such as Nivolumab and Pembrolizumab has shifted the paradigm of current HCC treatment, and the monotherapy or in combination with Lenvatinib or Sorafenib has significantly extended overall survival or progression-free survival in a large portion of patients. A combination of programmed cell death ligand-1 (PD-L1) inhibitor Atezolizumab with a vascular endothelial growth factor (VEGF) inhibitor, Bevacizumab, has recently achieved promising outcome in unresectable HCC patients. Other immunotherapy, such as chimeric antigen receptor T (CAR-T) cell therapy has achieved an evolutional success in hematologic malignancies, and has extended its use in deadly solid tumors, such as HCC. Although there exist various barriers, novel approaches are developed to move potential adoptive T cell therapy strategies, including cytokine-induced killer (CIK) cells, tumor-infiltrating lymphocytes (TIL), T cell receptor (TCR) T cells, CAR-T cells, to clinical application.
除索拉非尼外,仑伐替尼等几种分子靶向药物也可用于治疗晚期肝癌。纳武利尤单抗和帕博利珠单抗等免疫检查点抑制剂的批准改变了当前 HCC 治疗的模式,仑伐替尼或索拉非尼单药或联合治疗在很大一部分患者中显著延长了总生存期或无进展生存期。程序性细胞死亡配体 1(PD-L1)抑制剂阿特珠单抗与血管内皮生长因子(VEGF)抑制剂贝伐珠单抗联合用于不可切除 HCC 患者,最近取得了令人鼓舞的结果。嵌合抗原受体 T(CAR-T)细胞疗法等其他免疫疗法在血液恶性肿瘤中取得了显著成功,并已将其应用于 HCC 等致命实体肿瘤。尽管存在各种障碍,但为推动潜在的过继性 T 细胞治疗策略(包括细胞因子诱导的杀伤(CIK)细胞、肿瘤浸润淋巴细胞(TIL)、T 细胞受体(TCR)T 细胞、CAR-T 细胞)的临床应用,已开发出各种新方法。