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Pharmaceuticals
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Novel Therapeutic Target for Hepatocellular Carcinoma
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Novel Therapeutic Target for Hepatocellular Carcinoma

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 6508

Special Issue Editors

Prof. Dr. Guohui Wan

E-Mail Website
Guest Editor
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
Interests: therapeutic target; drug resistance; epigenetic regulation; immunotherapy
Dr. Xiaolei Zhang

E-Mail Website
Guest Editor
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
Interests: Targeted Therapy, Immunotherapy, tumor microenvironment, cancer metabolism

Special Issue Information

Dear Colleagues,

The treatment of hepatocellular carcinoma (HCC) has undergone a dramatic transformation in recent years with the development of targeted therapy and immunotherapy. Tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) and systemic chemotherapy are commonly used for patients with advanced HCC, and have been shown to improve their overall survival. After sorafenib was developed and marketed in 2017, four successive TKIs were launched, including the first-line drug Lenvatinib, and the second- and the third-line drugs regorafenib, cabozantinib and ramucirumab. In addition, immunotherapy-based combination therapies have been developed as successful first-line therapy options for advanced HCC, and exhibit favorable toxicity and enhanced efficacy. Combinations of either atezolizumab and bevacizumab or tremelimumab and durvalumab have shown improved overall survival compared to TKI alone, and they have served as novel therapeutic strategies for advanced HCC. However, some patients’ immune microenvironments are not suited to these therapies. These restraints highlight the need for novel therapeutic targets to improve current approaches, or more compounds to serve as reservoirs of novel therapeutic agents. 

In this Special Issue, we welcome original research articles and reviews focused on novel therapeutic targets, molecular mechanisms, compounds and therapeutic approaches for the treatment of HCC.

Prof. Dr. Guohui Wan
Dr. Xiaolei Zhang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • therapeutic targets
  • hepatocellular carcinoma
  • immunotherapy
  • tyrosine kinase inhibitors
  • microenvironment
  • drug resistance

Published Papers (3 papers)

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Research

17 pages, 14450 KiB  
Article
Inducing the Abscopal Effect in Liver Cancer Treatment: The Impact of Microwave Ablation Power Levels and PD-1 Antibody Therapy
by Changli Liao, Guiyuan Zhang, Ruotong Huang, Linyuan Zeng, Bin Chen, Haitao Dai, Keyu Tang, Run Lin and Yonghui Huang
Pharmaceuticals 2023, 16(12), 1672; https://doi.org/10.3390/ph16121672 - 30 Nov 2023
Viewed by 995
Abstract
Microwave ablation (MWA) is an effective treatment for liver cancer (LC), but its impact on distant tumors remains to be fully elucidated. This study investigated the abscopal effects triggered by MWA treatment of LC, at different power levels and with or without combined [...] Read more.
Microwave ablation (MWA) is an effective treatment for liver cancer (LC), but its impact on distant tumors remains to be fully elucidated. This study investigated the abscopal effects triggered by MWA treatment of LC, at different power levels and with or without combined immune checkpoint inhibition (ICI). We established a mouse model with bilateral subcutaneous LC and applied MWA of varied power levels to ablate the right-sided tumor, with or without immunotherapy. Left-sided tumor growth was monitored to assess the abscopal effect. Immune cell infiltration and distant tumor neovascularization were quantified via immunohistochemistry, revealing insights into the tumor microenvironment and neovascularization status. Th1- and Th2-type cytokine concentrations in peripheral blood were measured using ELISA to evaluate systemic immunological changes. It was found that MWA alone, especially at lower power, promoted distant tumor growth. On the contrary, combining high-power MWA with anti-programmed death (PD)-1 therapy promoted CD8+ T-cell infiltration, reduced regulatory T-cell infiltration, upregulated a Th1-type cytokine (TNF-α) in peripheral blood, and inhibited distant tumor growth. In summary, combining high-power MWA with ICI significantly enhances systemic antitumor immune responses and activates the abscopal effect, offering a facile and robust strategy for improving treatment outcomes. Full article
(This article belongs to the Special Issue Novel Therapeutic Target for Hepatocellular Carcinoma)
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19 pages, 10823 KiB  
Article
Lactylation-Related Gene Signature Effectively Predicts Prognosis and Treatment Responsiveness in Hepatocellular Carcinoma
by Zhe Cheng, Huichao Huang, Maoyu Li, Xujun Liang, Yuying Tan and Yongheng Chen
Pharmaceuticals 2023, 16(5), 644; https://doi.org/10.3390/ph16050644 - 25 Apr 2023
Cited by 8 | Viewed by 3287
Abstract
Background: Hepatocellular carcinoma (HCC) is a malignant tumor associated with high morbidity and mortality. Therefore, it is of great importance to develop effective prognostic models and guide clinical treatment in HCC. Protein lactylation is found in HCC tumors and is associated with HCC [...] Read more.
Background: Hepatocellular carcinoma (HCC) is a malignant tumor associated with high morbidity and mortality. Therefore, it is of great importance to develop effective prognostic models and guide clinical treatment in HCC. Protein lactylation is found in HCC tumors and is associated with HCC progression. Methods: The expression levels of lactylation-related genes were identified from the TCGA database. A lactylation-related gene signature was constructed using LASSO regression. The prognostic value of the model was assessed and further validated in the ICGC cohort, with the patients split into two groups based on risk score. Glycolysis and immune pathways, treatment responsiveness, and the mutation of signature genes were analyzed. The correlation between PKM2 expression and the clinical characteristics was investigated. Results: Sixteen prognostic differentially expressed lactylation-related genes were identified. An 8-gene signature was constructed and validated. Patients with higher risk scores had poorer clinical outcomes. The two groups were different in immune cell abundance. The high-risk group patients were more sensitive to most chemical drugs and sorafenib, while the low-risk group patients were more sensitive to some targeted drugs such as lapatinib and FH535. Moreover, the low-risk group had a higher TIDE score and was more sensitive to immunotherapy. PKM2 expression correlated with clinical characteristics and immune cell abundance in the HCC samples. Conclusions: The lactylation-related model exhibited robust predictive efficiency in HCC. The glycolysis pathway was enriched in the HCC tumor samples. A low-risk score indicated better treatment response to most targeted drugs and immunotherapy. The lactylation-related gene signature could be used as a biomarker for the effective clinical treatment of HCC. Full article
(This article belongs to the Special Issue Novel Therapeutic Target for Hepatocellular Carcinoma)
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16 pages, 6814 KiB  
Article
Inhibition of FGFR2 Signaling by Cynaroside Attenuates Liver Fibrosis
by Qilin Meng, Lin Luo, Minghua Lei, Zhiqi Chen, Yuanmeng Sun, Xue Chen, Zhaodong Zhai, Yibo Zhang, Jieqiong Cao, Zijian Su, Fu Li, Jingsheng Li, An Hong and Xiaojia Chen
Pharmaceuticals 2023, 16(4), 548; https://doi.org/10.3390/ph16040548 - 06 Apr 2023
Cited by 1 | Viewed by 1662
Abstract
Liver fibrosis represents a significant health hazard with a high morbidity rate and an increased risk of liver cancer. Targeting overactivated Fibroblast growth factor receptor 2 (FGFR2) is a promising strategy to counteract collagen accumulation during liver fibrosis. However, there is a shortage [...] Read more.
Liver fibrosis represents a significant health hazard with a high morbidity rate and an increased risk of liver cancer. Targeting overactivated Fibroblast growth factor receptor 2 (FGFR2) is a promising strategy to counteract collagen accumulation during liver fibrosis. However, there is a shortage of drugs to specifically block the activation of FGFR2 in liver fibrosis patients. Data mining, cell validation, and animal studies showed a positive correlation between FGFR2 overexpression and liver fibrosis development. Novel FGFR2 inhibitors were screened using a microarray-based high-throughput binding analysis. The effectiveness of each candidate was validated through simulated docking, binding affinity verification, single-point mutation validation, and in vitro kinase inhibition measurements to demonstrate the ability of each inhibitor to block the catalytic pocket and reverse FGFR2 overactivation. A specific FGFR2 inhibitor, cynaroside (CYN, also known as luteoloside), was screened based on the finding that FGFR2 promotes hepatic stellate cell (HSC) activation and collagen secretion in hepatocytes. The results from cellular assays showed that CYN can inhibit FGFR2 hyperactivation resulting from its overexpression and excessive basic fibroblast growth factor (bFGF), reducing HSC activation and collagen secretion in hepatocytes. Animal experiments on a carbon tetrachloride (CCl4) mouse model and a nonalcoholic steatohepatitis mouse model indicate that CYN treatment reduces liver fibrosis during fibrosis formation. These findings suggest that CYN prevents liver fibrosis formation at the cell level and in mouse models. Full article
(This article belongs to the Special Issue Novel Therapeutic Target for Hepatocellular Carcinoma)
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