Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.
Google Scholar
El-Serag HB, Siegel AB, Davila JA, Shaib YH, Cayton-Woody M, McBride R, et al. Treatment and outcomes of treating of hepatocellular carcinoma among medicare recipients in the United States: a population-based study. J Hepatol. 2006;44:158–66.
Google Scholar
Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380:1450–62.
Google Scholar
Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, et al. Hepatocellular carcinoma. Nat Rev Dis Prim. 2016;2:16018.
Google Scholar
Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Cheng AL, et al. Overall survival and objective response in advanced unresectable hepatocellular carcinoma: A subanalysis of the REFLECT study. J Hepatol. 2023;78:133–41.
Google Scholar
Chen Y, Dai S, Cheng CS, Chen L. Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives. J Hematol Oncol. 2024;17:130.
Google Scholar
Zschäbitz S, Grüllich C. et al. Lenvantinib: A Tyrosine Kinase Inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRα, KIT and RET. Recent Results Cancer Res. 2018;211:187–98.
Google Scholar
Phan P, Saikia BB, Sonnaila S, Agrawal S, Kumar TKS. et al. The saga of endocrine FGFs. Cells. 2021;10:2418.
Google Scholar
Matsuki M, Hoshi T, Yamamoto Y, Ikemori-Kawada M, Minoshima Y, Funahashi Y, et al. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med. 2018;7:2641–53.
Google Scholar
Lu C, Rong D, Zhang B, Zheng W, Wang X, Chen Z, et al. Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities. Mol Cancer. 2019;18:130.
Google Scholar
Sas Z, Cendrowicz E, Weinhäuser I, Rygiel TP. Tumor microenvironment of hepatocellular carcinoma: challenges and opportunities for new treatment options. Int J Mol Sci. 2022;23:3778.
Google Scholar
Lu Y, Yang A, Quan C, Pan Y, Zhang H, Li Y, et al. A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma. Nat Commun. 2022;13:4594.
Google Scholar
Lavie D, Ben-Shmuel A, Erez N, Scherz-Shouval R. Cancer-associated fibroblasts in the single-cell era. Nat Cancer. 2022;3:793–807.
Google Scholar
Song M, He J, Pan QZ, Yang J, Zhao J, Zhang YJ, et al. Cancer-associated fibroblast-mediated cellular crosstalk supports hepatocellular carcinoma progression. Hepatology. 2021;73:1717–35.
Google Scholar
Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20:174–86.
Google Scholar
Gascard P, Tlsty TD. Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev. 2016;30:1002–19.
Google Scholar
Procacci P, Moscheni C, Sartori P, Sommariva M, Gagliano N. Tumor⁻stroma cross-talk in human pancreatic ductal adenocarcinoma: a focus on the effect of the extracellular matrix on tumor cell phenotype and invasive potential. Cells. 2018;7:158.
Google Scholar
Affo S, Yu LX, Schwabe RF. The role of cancer-associated fibroblasts and fibrosis in liver cancer. Annu Rev Pathol. 2017;12:153–86.
Google Scholar
Lin Z, Li G, Jiang K, Li Z, Liu T. Cancer therapy resistance mediated by cancer-associated fibroblast-derived extracellular vesicles: biological mechanisms to clinical significance and implications. Mol Cancer. 2024;23:191.
Google Scholar
Tosatto SC, Bosello V, Fogolari F, Mauri P, Roveri A, Toppo S, et al. The catalytic site of glutathione peroxidases. Antioxid Redox Signal. 2008;10:1515–26.
Google Scholar
Ren Z, He Y, Yang Q, Guo J, Huang H, Li B, et al. A comprehensive analysis of the glutathione peroxidase 8 (GPX8) in human cancer. Front Oncol. 2022;12:812811.
Google Scholar
Yang ZS, Yang Q, Sun XX, Xiong K, Zhu XT, Wang YC, et al. GPX8 as a novel prognostic factor and potential therapeutic target in primary glioma. J Immunol Res. 2022;2022:8025055.
Google Scholar
Zhang X, Xu H, Zhang Y, Sun C, Li Z, Hu C, et al. Immunohistochemistry and bioinformatics identify GPX8 as a potential prognostic biomarker and target in human gastric cancer. Front Oncol. 2022;12:878546.
Google Scholar
Chen H, Xu L, Shan ZL, Chen S, Hu H. GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway. Cancer Cell Int. 2020;20:596.
Google Scholar
Khatib A, Solaimuthu B, Ben Yosef M, Abu Rmaileh A, Tanna M, Oren G, et al. The glutathione peroxidase 8 (GPX8)/IL-6/STAT3 axis is essential in maintaining an aggressive breast cancer phenotype. Proc Natl Acad Sci USA. 2020;117:21420–31.
Google Scholar
Xu YL, Yuan LW, Jiang XM, Su MX, Huang MY, Chen YC, et al. Glutathione peroxidase 8 expression on cancer cells and cancer-associated fibroblasts facilitates lung cancer metastasis. MedComm. 2022;3:e152.
Google Scholar
Dey A, Chitsaz F, Abbasi A, Misteli T, Ozato K. The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis. Proc Natl Acad Sci USA. 2003;100:8758–63.
Google Scholar
Cheng CL, Tsang FH, Wei L, Chen M, Chin DW, Shen J, et al. Bromodomain-containing protein BRPF1 is a therapeutic target for liver cancer. Commun Biol. 2021;4:888.
Google Scholar
Geng X, Chen H, Zhao L, Hu J, Yang W, Li G, et al. Cancer-associated fibroblast (CAF) heterogeneity and targeting therapy of CAFs in pancreatic cancer. Front Cell Dev Biol. 2021;9:655152.
Google Scholar
Arner EN, Rathmell JC. Metabolic programming and immune suppression in the tumor microenvironment. Cancer Cell. 2023;41:421–33.
Google Scholar
Ramming T, Hansen HG, Nagata K, Ellgaard L, Appenzeller-Herzog C. GPx8 peroxidase prevents leakage of H2O2 from the endoplasmic reticulum. Free Radic Biol Med. 2014;70:106–16.
Google Scholar
Lee HA, Chu KB, Moon EK, Quan FS. Glutathione peroxidase 8 suppression by histone deacetylase inhibitors enhances endoplasmic reticulum stress and cell death by oxidative stress in hepatocellular carcinoma cells. Antioxidants. 2021;10:1503.
Google Scholar
Yang N, Qu YJ, Cheng Y, Liang T, Zhang MN, Zhang D, et al. Endoplasmic reticulum stress regulates proliferation, migration and invasion of human ovarian cancer SKOV3 cells through PI3K/AKT/mTOR signaling pathway. Cancer Biomark. 2017;19:263–9.
Google Scholar
Li LJ, Chai Y, Guo XJ, Chu SL, Zhang LS. Effects of endoplasmic reticulum stress on autophagy and apoptosis of human leukemia cells via inhibition of the PI3K/AKT/mTOR signaling pathway. Mol Med Rep. 2018;17:7886–92.
Google Scholar
Xu Z, Wang X, Cheng H, Li J, Zhang X, Wang X. The role of MCT1 in tumor progression and targeted therapy: a comprehensive review. Front Immunol. 2025;16:1610466.
Google Scholar
Chen J, Huang Z, Chen Y, Tian H, Chai P, Shen Y, et al. Lactate and lactylation in cancer. Signal Transduct Target Ther. 2025;10:38.
Google Scholar
Lim M, Franses JW, Imperial R, Majeed U, Tsai J, Hsiehchen D. EGFR/ERBB2 amplifications and alterations associated with resistance to lenvatinib in hepatocellular carcinoma. Gastroenterology. 2023;164:1006–8.e3.
Google Scholar
Zhang F, Ma Y, Li D, Wei J, Chen K, Zhang E, et al. Cancer associated fibroblasts and metabolic reprogramming: unraveling the intricate crosstalk in tumor evolution. J Hematol Oncol. 2024;17:80.
Google Scholar
Brechbuhl HM, Finlay-Schultz J, Yamamoto TM, Gillen AE, Cittelly DM, Tan AC, et al. Fibroblast subtypes regulate responsiveness of luminal breast cancer to estrogen. Clin Cancer Res. 2017;23:1710–21.
Google Scholar
Pelon F, Bourachot B, Kieffer Y, Magagna I, Mermet-Meillon F, Bonnet I, et al. Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nat Commun. 2020;11:404.
Google Scholar
Labernadie A, Kato T, Brugués A, Serra-Picamal X, Derzsi S, Arwert E, et al. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat Cell Biol. 2017;19:224–37.
Google Scholar
Zhan J, Li M, Li L, Zeng TT, Liu J, Chen Q, et al. Targeting LTBP2 derived from cancer-associated fibroblasts sensitizes esophageal squamous cell carcinoma to chemotherapy. Cancer Res. 2025;85:2412–28.
Google Scholar
Zhang J, Liu Y, Guo Y, Zhao Q. GPX8 promotes migration and invasion by regulating epithelial characteristics in non-small cell lung cancer. Thorac Cancer. 2020;11:3299–308.
Google Scholar
Jagust P, Alcalá S, Sainz B Jr, Heeschen C, Sancho P. Glutathione metabolism is essential for self-renewal and chemoresistance of pancreatic cancer stem cells. World J Stem Cells. 2020;12:1410–28.
Google Scholar
Tao CY, Wu XL, Song SS, Tang Z, Zhou YF, Tian MX, et al. Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration. Cell Oncol. 2024;47:1391–403.
Google Scholar
Halford S, Veal GJ, Wedge SR, Payne GS, Bacon CM, Sloan P, et al. A phase I Dose-escalation Study of AZD3965, an oral monocarboxylate transporter 1 inhibitor, in patients with advanced cancer. Clin Cancer Res. 2023;29:1429–39.
Google Scholar

