Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC

Cancers

Ka-On Lam¹  Bryan Li²  JoanneWing Yan Chiu²  Roland Leung²  GerryGin Wai Kwok²  Thomas Yau²  Yawen Dong²  JeffreySum Lung Wong²  TanTo Cheung³  Ryohichi Sugimura⁴ 

[1] Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China;Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China;Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China;School of Biomedical Science, The University of Hong Kong, Hong Kong, China;

关键词: hepatocellular carcinoma;    biomarker;    checkpoint inhibitors;    combination therapy;    targeted therapy;    precision medicine;   

DOI  :  10.3390/cancers13081949

来源: DOAJ

【 摘 要 】

Advanced, unresectable hepatocellular carcinoma has a dismal outcome. Multiple immune checkpoint inhibitors (ICIs) targeting the programmed-cell death 1 pathway (PD-1/L1) have been approved for the treatment of advanced HCC. However, outcomes remain undesirable and unpredictable on a patient-to-patient basis. The combination of anti-PD-1/L1 with alternative agents, chiefly cytotoxic T-lymphocyte antigen-4 (CTLA-4) ICIs or agents targeting other oncogenic pathways such as the vascular endothelial growth factor (VEGF) pathway and the c-MET pathway, has, in addition to the benefit of directly targeting alterative oncogenic pathways, in vitro evidence of synergism through altering the genomic and function signatures of T cells and expression of immune checkpoints. Several trials have been completed or are underway evaluating such combinations. Finally, studies utilizing transcriptomics and organoids are underway to establish biomarkers to predict ICI response. This review aims to discuss the biological rationale and clinical advances in ICI-based combinations in HCCs, as well as the progress and prospects of the search for the aforementioned biomarkers in ICI treatment of HCC.

【 授权许可】

Unknown