Review
Oncology
Yijun Wang, Danfei Liu, Tongyue Zhang, Limin Xia
Summary: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, ranking third in cancer deaths worldwide. Studies have focused on developing tyrosine kinase inhibitors (TKIs) to target aberrant pathways in HCC, but outcomes are unsatisfactory due to resistance and adverse effects. The fibroblast growth factor (FGF) family and its receptors (FGFR) play crucial roles in various biological processes and are also implicated in HCC. Anti-FGF/FGFR therapies show promising benefits for cancer patients with FGF signaling alterations, and new multi-kinase inhibitors targeting FGF signaling are under investigation for HCC treatment.
Article
Pharmacology & Pharmacy
Yuting Wu, Xiangbo Xu, Mingyue Liu, Xiaochun Qin, Qiong Wu, Huaiwei Ding, Qingchun Zhao
Summary: This study identified a novel PI3Ki (DZW-310) with strong anti-HCC activity. DZW-310 significantly inhibited HCC cell growth by promoting intrinsic apoptosis and G0/G1 phase cell arrest, and reduced angiogenesis by regulating the HIF-1 alpha/VEGFA axis. Mechanistically, DZW-310 acted as a PI3Ki by targeting PI3K alpha and deactivating the PI3K/AKT/mTOR pathway, demonstrating its potential as a promising therapeutic agent for HCC.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Oncology
Mikkel G. Terp, Kirstine Jacobsen, Miguel Angel Molina, Niki Karachaliou, Hans C. Beck, Jordi Bertran-Alamillo, Ana Gimenez-Capitan, Andres F. Cardona, Rafael Rosell, Henrik J. Ditzel
Summary: Resistance to EGFR tyrosine kinase inhibitors (TKIs) in NSCLC patients is often associated with increased FGFR1 expression and Akt activation, leading to the development of targeted therapy strategies for overcoming resistance. Combination therapy targeting both FGFR and Akt has shown superior growth inhibition of resistant cells in vitro and in vivo, providing a promising rationale for future clinical trials in NSCLC patients.
NPJ PRECISION ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Zhanchao Tao, Yue Cui, Xilong Xu, Ting Han
Summary: Aberrant FGF19 signaling through FGFR4 and KLB plays a driving role in hepatocellular carcinoma. Selective inhibition of FGFR4 alone is not sufficient to inhibit cell proliferation and tumor growth in FGF19-positive HCC, while genetic inactivation of KLB results in a more severe fitness defect. KLB associates with FGFR3 and FGFR4 to mediate the prosurvival functions of FGF19. FGFR3 restricts the activity of FGFR4-selective inhibitors, and pan-FGFR inhibitor erdafitinib is more potent in suppressing the growth and survival of FGF19-positive HCC cells. FGFR3 is prevalently coexpressed with FGFR4 and KLB in FGF19-positive HCC cases, suggesting FGFR redundancy as a common mechanism underlying resistance to FGFR4 inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Integrative & Complementary Medicine
Tarek El-Sewedy, Afrah Fatthi Salama, Amro E. Mohamed, Nashwa M. Elbaioumy, Ali H. El-Far, Aisha Nawaf Albalawi, Alaa Elmetwalli
Summary: This study found a synergistic effect between amygdalin and sorafenib in targeting AMPK/mTOR and BCL-2, which may potentially inhibit angiogenesis and induce apoptosis in HepG2 cells. The findings suggest that amygdalin could be a potential alternative therapeutic option for HCC.
BMC COMPLEMENTARY MEDICINE AND THERAPIES
(2023)
Article
Biotechnology & Applied Microbiology
Christos Dimitrakopoulos, Sravanth Kumar Hindupur, Marco Colombi, Dritan Liko, Charlotte K. Y. Ng, Salvatore Piscuoglio, Jonas Behr, Ariane L. Moore, Jochen Singer, Hans-Joachim Ruscheweyh, Matthias S. Matter, Dirk Mossmann, Luigi M. Terracciano, Michael N. Hall, Niko Beerenwinkel
Summary: This study explores the functional consequences of genetic aberrations in hepatocellular carcinoma through analyzing the transcriptome, proteome, and phosphoproteome. It identifies potential therapeutic targets such as YAP1 and GRB2 signaling pathways, as well as pathways regulating histone acetylation in HCC with hyperactive mTOR signaling.
Article
Medicine, Research & Experimental
Yuchen Jiang, Qinghe Zeng, Qinghui Jiang, Xia Peng, Jing Gao, Haiyan Wan, Luting Wang, Yinglei Gao, Xiaoyu Zhou, Dongze Lin, Hanyi Feng, Sheng Liang, Hu Zhou, Jian Ding, Jing Ai, Ruimin Huang
Summary: In this study, the researchers investigated the molecular mechanism and radiological phenotype of FGFR-targeted therapy in cancer patients. They found that FGFR inhibition can decrease the accumulation of F-18-FDG in FGFR-sensitive cancer cell lines by downregulating HK2 expression. They also demonstrated the effectiveness of using F-18-FDG PET imaging to differentiate between FGFRi-sensitive and resistant tumor xenografts. These findings suggest that using F-18-FDG PET as a biomarker-based imaging strategy can help assess the response and resistance to FGFR inhibition in cancer patients.
Article
Biochemistry & Molecular Biology
Runjie Song, Shuoqian Ma, Jiajia Xu, Xin Ren, Peilan Guo, Huijiao Liu, Peng Li, Fan Yin, Mei Liu, Qiang Wang, Lei Yu, Jiali Liu, Binwei Duan, Nafis A. Rahman, Slawomir Wolczynski, Guangming Li, Xiangdong Li
Summary: This study aims to elucidate the potential role and molecular mechanism of circZKSaa in the regulation of hepatocellular carcinoma (HCC) progression. Through a series of experiments, it was found that circZKSaa inhibited HCC progression and sensitized HCC cells to sorafenib. Furthermore, the high expression of cicZKSCAN1 in sorafenib-treated HCC cells was regulated by QKI-5. These findings demonstrate that circZKSaa has the potential to serve as a therapeutic target and biomarker for HCC treatment.
Article
Biochemistry & Molecular Biology
Xiaoling Zhang, Hao Liu, Haidong Wang, Rongjie Zhao, Qian Lu, Yunlong Liu, Yicheng Han, Hongming Pan, Weidong Han
Summary: This study found that b3galt5 is highly expressed in hepatocellular carcinoma (HCC) and associated with poor prognosis. It promotes the proliferation and survival of HCC cells and activates the mTOR/p70s6k pathway to enhance glycolysis through O-linked glycosylation modification. Inhibition of p70s6k reduces glycolysis in b3galt5-overexpressing cells. This study uncovers a novel mechanism and potential therapy target for HCC.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Peifang Qin, Jianguo Yan, Haitao Huang, Qi Wang, Mao Li, Yuting Zhang, Jiahui Wang, Tingting Jiang, Xiaoling Zhang, Yali Zhou
Summary: Equilibrative nucleoside transporter 3 (ENT3), a member of the solute carrier family 29, plays an important role in hepatocellular carcinoma (HCC). It is upregulated in HCC and associated with poor prognosis and clinical features. Knockdown of ENT3 inhibits cell proliferation, migration, and invasion, and promotes apoptosis through inhibition of the AKT/mTOR signaling pathway.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Immunology
Wenshu Tang, Jingying Zhou, Weiqin Yang, Yu Feng, Haoran Wu, Myth T. S. Mok, Lingyun Zhang, Zhixian Liang, Xiaoyu Liu, Zhewen Xiong, Xuezhen Zeng, Jing Wang, Jiahuan Lu, Jingqing Li, Hanyong Sun, Xiaoyu Tian, Philip Chun Yeung, Yong Hou, Heung Man Lee, Candice C. H. Lam, Howard H. W. Leung, Anthony W. H. Chan, Ka Fai To, John Wong, Paul B. S. Lai, Kelvin K. C. Ng, Simon K. H. Wong, Vincent W. S. Wong, Alice P. S. Kong, Joseph J. Y. Sung, Alfred S. L. Cheng
Summary: Obesity and hypercholesterolemia are major risk factors for hepatocellular carcinoma. This study found that obesity leads to hepatic cholesterol accumulation, which suppresses natural killer T (NKT) cell-mediated antitumor immunosurveillance. By lowering cholesterol and inhibiting cholesterol biosynthesis, the function of NKT cells can be restored to prevent HCC development promoted by obesity.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shuangda Li, Yu Qi, Yiran Huang, Yanru Guo, Tong Huang, Li Jia
Summary: The study revealed that SNHG16, through exosomes, enhances the proliferative, migratory, and angiogenic effects of HCC cells on endothelial cells, further activating the PI3K/Akt/mTOR pathway to promote tumor growth. Exosomal SNHG16 may serve as a therapeutic target for anti-angiogenesis in HCC progression.
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Review
Cell Biology
Yongyuan He, Yinghong Su, Chengcheng Duan, Siyuan Wang, Wei He, Yingting Zhang, Xiaofei An, Ming He
Summary: With the global aging population, nonalcoholic fatty liver disease (NAFLD) has dramatically increased in recent decades. It is a progressive disease that ranges from simple fatty liver to liver cirrhosis and hepatocellular carcinoma (HCC). Aging plays a crucial role in the development and progression of NAFLD, HCC, and other age-related liver diseases. The involvement of senescent cells and aging-related factors, such as NAD+, sirtuins, and mTOR, in the development of NAFLD has been explored, although their significance remains underestimated. This review summarizes current research on the roles of aging, cellular senescence, and aging-related factors in the evolution of NAFLD to HCC, with the aim of identifying potential therapeutic targets for aging-related NAFLD and its progression.
AGEING RESEARCH REVIEWS
(2023)
Article
Oncology
Zhibin Mei, Xingxing Gao, Caixu Pan, Qinchuan Wu, Shuai Wang, Junjie Qian, Zhentian Xu, Kangdi Xu, Lin Zhou, Shushen Zhen
Summary: This study established an orthotopic hepa1-6 mouse model treated with lenvatinib to investigate the effects of lenvatinib on PD1(+) CD8(+) T cells. The results showed that lenvatinib increased the proportion of TCF-1(+) in PD1(+) CD8(+) T cells and promoted their proliferation. It also upregulated the expression of granzyme B on PD1(+) CD8(+) T cells. The activation of the mTOR pathway and VEGFR2 inhibition played important roles in the antitumor efficacy of lenvatinib.
Review
Chemistry, Medicinal
Suzana Bracic Tomazic, Christoph Schatz, Johannes Haybaeck
Summary: The article covers the role of the mTOR signaling pathway in the development of HCC and the research progress on related factors. Risk factors play a crucial role in dysregulation of the pathway, and the quantity of specific factors in patient samples can predict HCC recurrence and treatment outcomes.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)