Hepatocellular carcinoma: signaling pathways and therapeutic advances
Abstract Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% of liver cancer cases and is primarily linked to factors incluidng aflatoxin, hepat...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-02-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-024-02075-w |
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| author | Jiaojiao Zheng Siying Wang Lei Xia Zhen Sun Kui Ming Chan René Bernards Wenxin Qin Jinhong Chen Qiang Xia Haojie Jin |
| author_facet | Jiaojiao Zheng Siying Wang Lei Xia Zhen Sun Kui Ming Chan René Bernards Wenxin Qin Jinhong Chen Qiang Xia Haojie Jin |
| author_sort | Jiaojiao Zheng |
| collection | DOAJ |
| description | Abstract Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% of liver cancer cases and is primarily linked to factors incluidng aflatoxin, hepatitis B (HBV) and C (HCV), and metabolic disorders. There are no obvious symptoms in the early stage of HCC, which often leads to delays in diagnosis. Therefore, HCC patients usually present with tumors in advanced and incurable stages. Several signaling pathways are dis-regulated in HCC and cause uncontrolled cell propagation, metastasis, and recurrence of HCC. Beyond the frequently altered and therapeutically targeted receptor tyrosine kinase (RTK) pathways in HCC, pathways involved in cell differentiation, telomere regulation, epigenetic modification and stress response also provide therapeutic potential. Investigating the key signaling pathways and their inhibitors is pivotal for achieving therapeutic advancements in the management of HCC. At present, the primary therapeutic approaches for advanced HCC are tyrosine kinase inhibitors (TKI), immune checkpoint inhibitors (ICI), and combination regimens. New trials are investigating combination therapies involving ICIs and TKIs or anti-VEGF (endothelial growth factor) therapies, as well as combinations of two immunotherapy regimens. The outcomes of these trials are expected to revolutionize HCC management across all stages. Here, we provide here a comprehensive review of cellular signaling pathways, their therapeutic potential, evidence derived from late-stage clinical trials in HCC and discuss the concepts underlying earlier clinical trials, biomarker identification, and the development of more effective therapeutics for HCC. |
| format | Article |
| id | doaj-art-ffef49c6f5214149aa40fc5c4442f7c4 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-ffef49c6f5214149aa40fc5c4442f7c42025-02-09T12:56:28ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-02-0110114310.1038/s41392-024-02075-wHepatocellular carcinoma: signaling pathways and therapeutic advancesJiaojiao Zheng0Siying Wang1Lei Xia2Zhen Sun3Kui Ming Chan4René Bernards5Wenxin Qin6Jinhong Chen7Qiang Xia8Haojie Jin9State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Biomedical Sciences, City University of Hong KongState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Huashan Hospital, Fudan UniversityDepartment of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of MedicineAbstract Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% of liver cancer cases and is primarily linked to factors incluidng aflatoxin, hepatitis B (HBV) and C (HCV), and metabolic disorders. There are no obvious symptoms in the early stage of HCC, which often leads to delays in diagnosis. Therefore, HCC patients usually present with tumors in advanced and incurable stages. Several signaling pathways are dis-regulated in HCC and cause uncontrolled cell propagation, metastasis, and recurrence of HCC. Beyond the frequently altered and therapeutically targeted receptor tyrosine kinase (RTK) pathways in HCC, pathways involved in cell differentiation, telomere regulation, epigenetic modification and stress response also provide therapeutic potential. Investigating the key signaling pathways and their inhibitors is pivotal for achieving therapeutic advancements in the management of HCC. At present, the primary therapeutic approaches for advanced HCC are tyrosine kinase inhibitors (TKI), immune checkpoint inhibitors (ICI), and combination regimens. New trials are investigating combination therapies involving ICIs and TKIs or anti-VEGF (endothelial growth factor) therapies, as well as combinations of two immunotherapy regimens. The outcomes of these trials are expected to revolutionize HCC management across all stages. Here, we provide here a comprehensive review of cellular signaling pathways, their therapeutic potential, evidence derived from late-stage clinical trials in HCC and discuss the concepts underlying earlier clinical trials, biomarker identification, and the development of more effective therapeutics for HCC.https://doi.org/10.1038/s41392-024-02075-w |
| spellingShingle | Jiaojiao Zheng Siying Wang Lei Xia Zhen Sun Kui Ming Chan René Bernards Wenxin Qin Jinhong Chen Qiang Xia Haojie Jin Hepatocellular carcinoma: signaling pathways and therapeutic advances Signal Transduction and Targeted Therapy |
| title | Hepatocellular carcinoma: signaling pathways and therapeutic advances |
| title_full | Hepatocellular carcinoma: signaling pathways and therapeutic advances |
| title_fullStr | Hepatocellular carcinoma: signaling pathways and therapeutic advances |
| title_full_unstemmed | Hepatocellular carcinoma: signaling pathways and therapeutic advances |
| title_short | Hepatocellular carcinoma: signaling pathways and therapeutic advances |
| title_sort | hepatocellular carcinoma signaling pathways and therapeutic advances |
| url | https://doi.org/10.1038/s41392-024-02075-w |
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