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A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Novel molecular targets in hepatocellular carcinoma
Ariel Ka-Man Chow1, Simon Wing-Lung Yau1, Lui Ng2
1School of Nursing and Health Studies, The Open University of Hong Kong, Hong Kong, China.
Abstract:
Globally, hepatocellular carcinoma (HCC) is a leading cause of cancer and cancer-related deaths. The therapeutic efficacy of locoregional and systemic treatment in patients with advanced HCC remains low, which results in a poor prognosis. The development of sorafenib for the treatment of HCC has resulted in a new era of molecular targeted therapy for this disease. However, the median overall survival was reported to be barely higher in the sorafenib treatment group than in the control group. Hence, in this review we describe the importance of developing more effective targeted therapies for the management of advanced HCC. Recent investigations of molecular signaling pathways in several cancers have provided some insights into developing molecular therapies that target critical members of these signaling pathways. Proteins involved in the Hedgehog and Notch signaling pathways, Polo-like kinase 1, arginine, histone deacetylases and Glypican-3 can be potential targets in the treatment of HCC. Monotherapy has limited therapeutic efficacy due to the development of inhibitory feedback mechanisms and induction of chemoresistance. Thus, emphasis is now on the development of personalized and combination molecular targeted therapies that can serve as ideal therapeutic strategies for improved management of HCC.
Insights
Hepatocellular carcinoma (HCC) treatment needs better targeted therapies. Research highlights new molecular targets and combination strategies for improved patient outcomes in advanced HCC.
Area of Science:
- Hepatology
- Oncology
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) is a major global cancer burden with poor prognosis in advanced stages.
- Current locoregional and systemic treatments offer limited efficacy.
- Sorafenib, a molecular targeted therapy, has shown marginal survival benefits in advanced HCC.
Purpose of the Study:
- To review the importance of developing more effective targeted therapies for advanced HCC.
- To identify potential molecular targets within signaling pathways for HCC treatment.
- To emphasize the need for personalized and combination therapies.
Main Methods:
- Review of recent investigations into molecular signaling pathways in cancer.
- Identification of critical proteins and pathways implicated in HCC pathogenesis.
- Analysis of limitations of monotherapy and the potential of combination strategies.
Main Results:
- Hedgehog and Notch signaling pathways, Polo-like kinase 1, arginine, histone deacetylases, and Glypican-3 are identified as potential therapeutic targets.
- Monotherapy faces challenges due to feedback mechanisms and chemoresistance.
- Personalized and combination molecular targeted therapies are crucial for improved management.
Conclusions:
- Advanced HCC requires novel and more effective targeted therapeutic strategies.
- Targeting specific molecular pathways offers promising avenues for HCC treatment.
- Combination and personalized approaches are essential for overcoming therapeutic resistance and improving survival in HCC patients.
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