Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC
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-pati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/8/1949 |
| _version_ | 1797537276090122240 |
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| author | Yawen Dong Jeffrey Sum Lung Wong Ryohichi Sugimura Ka-On Lam Bryan Li Gerry Gin Wai Kwok Roland Leung Joanne Wing Yan Chiu Tan To Cheung Thomas Yau |
| author_facet | Yawen Dong Jeffrey Sum Lung Wong Ryohichi Sugimura Ka-On Lam Bryan Li Gerry Gin Wai Kwok Roland Leung Joanne Wing Yan Chiu Tan To Cheung Thomas Yau |
| author_sort | Yawen Dong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:12:49Z |
| format | Article |
| id | doaj.art-b3edd1f83c5d439ba0f205e3c2717530 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:12:49Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b3edd1f83c5d439ba0f205e3c27175302023-11-21T16:04:53ZengMDPI AGCancers2072-66942021-04-01138194910.3390/cancers13081949Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCCYawen Dong0Jeffrey Sum Lung Wong1Ryohichi Sugimura2Ka-On Lam3Bryan Li4Gerry Gin Wai Kwok5Roland Leung6Joanne Wing Yan Chiu7Tan To Cheung8Thomas Yau9Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Science, The University of Hong Kong, Hong Kong, ChinaDepartment of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaDepartment of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, ChinaAdvanced, 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.https://www.mdpi.com/2072-6694/13/8/1949hepatocellular carcinomabiomarkercheckpoint inhibitorscombination therapytargeted therapyprecision medicine |
| spellingShingle | Yawen Dong Jeffrey Sum Lung Wong Ryohichi Sugimura Ka-On Lam Bryan Li Gerry Gin Wai Kwok Roland Leung Joanne Wing Yan Chiu Tan To Cheung Thomas Yau Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC Cancers hepatocellular carcinoma biomarker checkpoint inhibitors combination therapy targeted therapy precision medicine |
| title | Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC |
| title_full | Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC |
| title_fullStr | Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC |
| title_full_unstemmed | Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC |
| title_short | Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC |
| title_sort | recent advances and future prospects in immune checkpoint ici based combination therapy for advanced hcc |
| topic | hepatocellular carcinoma biomarker checkpoint inhibitors combination therapy targeted therapy precision medicine |
| url | https://www.mdpi.com/2072-6694/13/8/1949 |
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