Hypoxia As a Target for Combination with Transarterial Chemoembolization in Hepatocellular Carcinoma

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2024 Aug 29

PMID 39204162

Authors

Zizhuo Wang

Qing Li

Bin Liang

Affiliations

Soon will be listed here.

Abstract

Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proven to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable HCC. However, TACE-induced hypoxia regulates tumor angiogenesis, energy metabolism, epithelial-mesenchymal transition (EMT), and immune processes through hypoxia-inducible factor 1 (HIF-1), which may have adverse effects on the therapeutic efficacy of TACE. Hypoxia has emerged as a promising target for combination with TACE in the treatment of HCC. This review summarizes the impact of hypoxia on HCC tumor biology and the adverse effects of TACE-induced hypoxia on its therapeutic efficacy, highlighting the therapeutic potential of hypoxia-targeted therapy in combination with TACE for HCC.

Citing Articles

Targeting Glycolytic Enzymes with 3-Bromopyruvic Acid to Enhance the Efficacy of Interventional Embolization in Hepatocellular Carcinoma.

Wang M, Wu X, Cheng X, Guo X, Zeng Z, Song S Curr Med Sci. 2025; 45(1):114-121.

PMID: 39982645 DOI: 10.1007/s11596-025-00009-3.

References

Sugden M, Holness M . Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am J Physiol Endocrinol Metab. 2003; 284(5):E855-62. DOI: 10.1152/ajpendo.00526.2002. View

Harris A . Hypoxia--a key regulatory factor in tumour growth. Nat Rev Cancer. 2002; 2(1):38-47. DOI: 10.1038/nrc704. View

Gaba R, Lewandowski R, Hickey R, Baerlocher M, Cohen E, Dariushnia S . Transcatheter Therapy for Hepatic Malignancy: Standardization of Terminology and Reporting Criteria. J Vasc Interv Radiol. 2016; 27(4):457-73. DOI: 10.1016/j.jvir.2015.12.752. View

Petrillo M, Patella F, Pesapane F, Suter M, Ierardi A, Angileri S . Hypoxia and tumor angiogenesis in the era of hepatocellular carcinoma transarterial loco-regional treatments. Future Oncol. 2018; 14(28):2957-2967. DOI: 10.2217/fon-2017-0739. View

Yang Z, Zhu Y, Dong Z, Hao Y, Wang C, Li Q . Engineering bioluminescent bacteria to boost photodynamic therapy and systemic anti-tumor immunity for synergistic cancer treatment. Biomaterials. 2022; 281:121332. DOI: 10.1016/j.biomaterials.2021.121332. View

Fu Y, Liu S, Zeng S, Shen H . From bench to bed: the tumor immune microenvironment and current immunotherapeutic strategies for hepatocellular carcinoma. J Exp Clin Cancer Res. 2019; 38(1):396. PMC: 6734524. DOI: 10.1186/s13046-019-1396-4. View

Llovet J, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4):378-90. DOI: 10.1056/NEJMoa0708857. View

Mise M, Arii S, Higashituji H, Furutani M, Niwano M, Harada T . Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor. Hepatology. 1996; 23(3):455-64. DOI: 10.1053/jhep.1996.v23.pm0008617424. View

Li Q, Liu Y, Guo X, Zhang L, Li L, Zhao D . Tirapazamine-loaded CalliSpheres microspheres enhance synergy between tirapazamine and embolization against liver cancer in an animal model. Biomed Pharmacother. 2022; 151:113123. DOI: 10.1016/j.biopha.2022.113123. View

10.

Semenza G . Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci. 2012; 33(4):207-14. PMC: 3437546. DOI: 10.1016/j.tips.2012.01.005. View

11.

Semenza G . Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003; 3(10):721-32. DOI: 10.1038/nrc1187. View

12.

Cao Y, Xiong F, Kan X, Guo X, Ouyang T, Wang R . Transarterial viroembolization improves the therapeutic efficacy of immune-excluded liver cancer: Three birds with one stone. Pharmacol Res. 2022; 187:106581. DOI: 10.1016/j.phrs.2022.106581. View

13.

Wu T, Yao Y, Sun R, Wang H, Zhang J, Yin X . Arterial instillation of rapamycin in treatment of rabbit hepatic xenograft tumors and its effects on VEGF, iNOS, HIF-1α, Bcl-2, Bax expression and microvessel density. Sci Prog. 2021; 104(3):368504211026417. PMC: 10364938. DOI: 10.1177/00368504211026417. View

14.

Zhu H, Chen X, Luo S, Guan J, Zhang W, Zhang B . Involvement of hypoxia-inducible factor-1-alpha in multidrug resistance induced by hypoxia in HepG2 cells. J Exp Clin Cancer Res. 2006; 24(4):565-74. View

15.

Abbattista M, Jamieson S, Gu Y, Nickel J, Pullen S, Patterson A . Pre-clinical activity of PR-104 as monotherapy and in combination with sorafenib in hepatocellular carcinoma. Cancer Biol Ther. 2015; 16(4):610-22. PMC: 4622463. DOI: 10.1080/15384047.2015.1017171. View

16.

Gandara D, Lara Jr P, Goldberg Z, Le Q, Mack P, Lau D . Tirapazamine: prototype for a novel class of therapeutic agents targeting tumor hypoxia. Semin Oncol. 2002; 29(1 Suppl 4):102-9. DOI: 10.1053/sonc.2002.31531. View

17.

Zhu H, Wang D, Yuan T, Yan F, Zeng C, Dai X . Multikinase Inhibitor CT-707 Targets Liver Cancer by Interrupting the Hypoxia-Activated IGF-1R-YAP Axis. Cancer Res. 2018; 78(14):3995-4006. DOI: 10.1158/0008-5472.CAN-17-1548. View

18.

Tran N, Foster N, Mahipal A, Byrne T, Hubbard J, Silva A . Phase IB study of sorafenib and evofosfamide in patients with advanced hepatocellular and renal cell carcinomas (NCCTG N1135, Alliance). Invest New Drugs. 2021; 39(4):1072-1080. PMC: 8282689. DOI: 10.1007/s10637-021-01090-w. View

19.

Yan J, Shen F, Wang K, Wu M . Patients with advanced primary hepatocellular carcinoma treated by melatonin and transcatheter arterial chemoembolization: a prospective study. Hepatobiliary Pancreat Dis Int. 2003; 1(2):183-6. View

20.

Chen W, He C, Qiao N, Guo Z, Hu S, Song Y . Dual drugs decorated bacteria irradiate deep hypoxic tumor and arouse strong immune responses. Biomaterials. 2022; 286:121582. DOI: 10.1016/j.biomaterials.2022.121582. View