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Cited by 316Cancer, Hypoxia, and MetabolismHepatocellular Carcinoma Treatment and PrognosisFerroptosis and cancer prognosis

Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

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Bao, Macus Hao-Ran, Wong, Carmen Chak-Lui·2021·Cells
DOI 10.3390/cells10071715PMC PMC8304710
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Abstract

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

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  • Intratumoral hypoxia is a major driving force for cancer progression.

    “Intratumoral hypoxia is a major driving force for cancer progression (15–19).”

    From HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy (2022) · cites this paper as [15]

    Section 2 says intratumoral hypoxia in hepatocellular carcinoma induces metabolic changes that promote drug resistance. Section 3.1 links conditions in the tumor microenvironment to faster tumor progression. These passages support a role for hypoxia in progression, but do not establish that it is a major driving force for cancer progression generally. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Bao, M. H.-R., & Wong, C. C.-L.
Affiliations
University of Hong Kong (HK)
Corresponding author
Wong, Carmen Chak-Lui
ORCID
Wong, Carmen Chak-Lui
Venue
Cells
Publisher
MDPI AG
Published
2021-07-06
Volume
10
Issue
7
Pages
1715
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells10071715
PMC
PMC8304710
OpenAlex
W3178403391
Cited by
316
References
121
Citations by year
2026: 35 · 2025: 75 · 2024: 84 · 2023: 71 · 2022: 48 · 2021: 3
FWCI
6.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2019BT02Y198)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
Keywords
hepatocellular carcinoma, tumor hypoxia, metabolic reprogramming, drug resistance, hypoxia-inducible factor, combination therapy, liver cancer treatment
MeSH terms
Sorafenib, Nivolumab, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Immune Checkpoint Inhibitors, Hypoxia, Antineoplastic Agents, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, Hypoxia-Inducible Factor 1, alpha Subunit, Metabolic Networks and Pathways, Tumor Microenvironment, Antibodies, Monoclonal, Humanized, Cellular Reprogramming

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