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Signal transduction and targeted therapy
Feb 07, 2025;10 (1): 35.

Hepatocellular carcinoma: signaling pathways and therapeutic advances.

Jiaojiao Zheng, Siying Wang, Lei Xia, Zhen Sun, Kui Ming Chan, René Bernards, Wenxin Qin, Jinhong Chen, Qiang Xia, Haojie Jin
Author Information
  1. Jiaojiao Zheng: State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
  2. Siying Wang: State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
  3. Lei Xia: Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
  4. Zhen Sun: State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
  5. Kui Ming Chan: Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, PR China. ORCID
  6. René Bernards: State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. ORCID
  7. Wenxin Qin: State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. ORCID
  8. Jinhong Chen: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, PR China. jinhongch@hotmail.com. ORCID
  9. Qiang Xia: Department of Liver Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. xiaqiang@shsmu.edu.cn. ORCID
  10. Haojie Jin: State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. hjjin1986@shsci.org. ORCID
PMID: 39915447 DOI: 10.1038/s41392-024-02075-w

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.

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Grants

  1. 82222047, 82073039/National Natural Science Foundation of China (National Science Foundation of China)

MeSH Term

Humans
Carcinoma, Hepatocellular
Liver Neoplasms
Signal Transduction
Immune Checkpoint Inhibitors
Protein Kinase Inhibitors

Chemicals

Immune Checkpoint Inhibitors
Protein Kinase Inhibitors
Journal Article Review
Article has an altmetric score of 9

Word Cloud

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