Glyceraldehyde-3-Phosphate Dehydrogenase: A Promising Target for Molecular Therapy in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer, with an increasing mortality rate. Aberrant expression of fibroblast growth factor 19–fibroblast growth factor receptor 4 (FGF19–FGFR4) is reported to be an oncogenic-driver pathway for HCC patients. Thus, the FGF19–FGFR4 signaling pathway is a promising target for the treatment of HCC. Several pan-FGFR (1–4) and FGFR4-specific inhibitors are in different phases of clinical trials. In this review, we summarize the information, recent developments, binding modes, selectivity, and clinical trial phases of different available FGFR4/pan-FGF inhibitors. We also discuss future perspectives and highlight the points that should be addressed to improve the efficacy of these inhibitors.

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Targeted Therapies in the Treatment of Advanced Hepatocellular Carcinoma

Clinical Medicine Insights Oncology ◽

10.4137/cmo.s7633 ◽

2013 ◽

Vol 7 ◽

pp. CMO.S7633 ◽

Cited By ~ 14

Author(s):

Zhengyu Wei ◽

Cataldo Doria ◽

Yuan Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Targeted Therapies ◽

Recent Progress ◽

Systemic Treatment ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc ◽

The Third ◽

Promising Target ◽

Targeted Treatments ◽

Attractive Option

Hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer death. It has been a major worldwide health problem with more new cases being diagnosed each year. The current available therapies for patients with advanced HCC are extremely limited. Therefore, it is of great clinical interests to develop more effective therapies for systemic treatment of advanced HCC. Several promising target-based drugs have been tested in a number of clinical trials. One breakthrough of these efforts is the approved clinical use of sorafenib in patients with advanced HCC. Targeted therapies are becoming an attractive option for the treatment of advanced HCC. In this review, we summarize the most recent progress in clinical targeted treatments of advanced HCC.

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Molecular therapy for the treatment of hepatocellular carcinoma

British Journal of Cancer ◽

10.1038/sj.bjc.6604784 ◽

2008 ◽

Vol 100 (1) ◽

pp. 19-23 ◽

Cited By ~ 51

Author(s):

T F Greten ◽

F Korangy ◽

M P Manns ◽

N P Malek

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Therapy

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BZW2/5MP1 acts as a promising target in hepatocellular carcinoma

Journal of Cancer ◽

10.7150/jca.53282 ◽

2021 ◽

Vol 12 (17) ◽

pp. 5125-5135

Author(s):

Guoxiong Li ◽

Anqian Lu ◽

Anna Chen ◽

Shuang Geng ◽

Yu Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Promising Target

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The Role of TIM-3 in Hepatocellular Carcinoma: A Promising Target for Immunotherapy?

Frontiers in Oncology ◽

10.3389/fonc.2020.601661 ◽

2020 ◽

Vol 10 ◽

Author(s):

Mazdak Ganjalikhani Hakemi ◽

Morteza Jafarinia ◽

Mahdieh Azizi ◽

Mahsa Rezaeepoor ◽

Orkhan Isayev ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Checkpoint ◽

Cytotoxic T Lymphocyte ◽

Therapeutic Effects ◽

Promising Target ◽

Checkpoint Molecule ◽

Important Challenge ◽

Cell Death Protein ◽

Universal Health

One of the most common tumors in the world is hepatocellular carcinoma (HCC), and its mortality rates are still on the rise, so addressing it is considered an important challenge for universal health. Despite the various treatments that have been developed over the past decades, the prognosis for advanced liver cancer is still poor. Recently, tumor immunotherapy has opened new opportunities for suppression of tumor progression, recurrence, and metastasis. Besides this, investigation into this malignancy due to high immune checkpoint expression and the change of immunometabolic programming in immune cells and tumor cells is highly considered. Because anti-cytotoxic T lymphocyte–associated protein (CTLA)-4 antibodies and anti-programmed cell death protein (PD)-1 antibodies have shown therapeutic effects in various cancers, studies have shown that T cell immunoglobulin mucin-3 (TIM-3), a new immune checkpoint molecule, plays an important role in the development of HCC. In this review, we summarize the recent findings on signal transduction events of TIM-3, its role as a checkpoint target for HCC therapy, and the immunometabolic situation in the progression of HCC.

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Current immunotherapeutic strategies in hepatocellular carcinoma: recent advances and future directions

Therapeutic Advances in Gastroenterology ◽

10.1177/1756283x17722061 ◽

2017 ◽

Vol 10 (10) ◽

pp. 805-814 ◽

Cited By ~ 8

Author(s):

Hwi Young Kim ◽

Joong-Won Park

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Responses ◽

Cancer Vaccines ◽

Immune Checkpoint Blockade ◽

Recurrence Rates ◽

Future Directions ◽

Optimal Outcomes ◽

Recent Advances ◽

Promising Target ◽

Tumor Stages

Hepatocellular carcinoma (HCC) is a common and serious health problem with high mortality. Treatment for HCC remains largely unsatisfactory owing to its high recurrence rates and frequent accompanying cirrhosis. In addition, the unique immune environment of the liver promotes tolerance, which, in conjunction with immune evasion by the disease, makes HCC a less promising target for conventional immunotherapy. However, recent advances in the immunotherapy have led to novel approaches to overcome these obstacles by manipulating and enhancing tumor-specific immune responses against HCC by using various modalities, such as cancer vaccines and immune checkpoint blockade. These treatments have shown both safety and promising outcomes in patients with HCC of various etiologies and tumor stages. Furthermore, combined strategies have been assessed to achieve optimal outcomes, by using immunotherapies with or without conventional treatments. This review briefly covers the background, recent advances, current issues, and future perspectives on immunotherapy in the field of HCC treatment.

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Synergistic Effect of MiR-146a Mimic and Cetuximab on Hepatocellular Carcinoma Cells

BioMed Research International ◽

10.1155/2014/384121 ◽

2014 ◽

Vol 2014 ◽

pp. 1-15 ◽

Cited By ~ 7

Author(s):

Suning Huang ◽

Rongquan He ◽

Minhua Rong ◽

Yiwu Dang ◽

Gang Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Synergistic Effect ◽

Vital Role ◽

Molecular Therapy ◽

Therapy Strategy ◽

Formalin Fixed Paraffin Embedded ◽

Ffpe Tissues ◽

Hcc Cells

Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored thein vitroeffect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.

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Perspectives of Molecular Therapy-Targeted Mitochondrial Fission in Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2020/1039312 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Hanwen Zhang ◽

Yanshuo Ye ◽

Wei Li

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Dynamic Equilibrium ◽

Mitochondrial Fission ◽

Molecular Therapy ◽

Eukaryotic Cells ◽

Molecular Targeting ◽

Molecular Pathways ◽

Ros Homeostasis ◽

Dynamic Equilibrium State

Current advances of molecular-targeting therapies for hepatocellular carcinoma (HCC) have improved the overall survival significantly, whereas the results still remain unsatisfied. Recently, much attention has been focused on organelles, such as the mitochondria, to reveal novel strategies to control the cancers. The mitochondria are vital organelles which supply energy and maintain metabolism in most of the eukaryotic cells. They not only execute critical bioenergetic and biosynthetic functions but also regulate ROS homeostasis and apoptosis. Existing in a dynamic equilibrium state, mitochondria constantly undergo the fission and fusion processes in normal situation. Increasing evidences have showed that mitochondrial fission is highly related to the diseases and cancers. Distinctive works have proved the significant effects of mitochondrial fission on HCC behaviors and the crosstalks with other molecular pathways. Here, we provide an overview of the mitochondrial fission and the link with HCC, emphasizing on the underlying molecular pathways and several novel materials that modulate HCC behaviors.

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