Targeting the Thioredoxin System for Cancer Therapy
Abstract
Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-molecule TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx.
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Inhibition of Trx1 and Grx1 could have pro-apoptotic effects in cancer cells.
“Inhibition of Trx1 and Grx1 could, therefore, have pro-apoptotic effects in cancer cells23,29.”
From Inhibition of the glutaredoxin and thioredoxin systems and ribonucleotide reductase by mutant p53-targeting compound APR-246 (2018) · cites this paper as [29]
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Zhang, J., Yao, J., Peng, S., Li, X., & Fang, J. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.10.019 · Cited by 58 · see citing works
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Clinically Evaluated Cancer Drugs Inhibiting Redox Signaling
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Thioredoxin-dependent regulation of AIF-mediated DNA damage
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Current Progresses in Metal-based Anticancer Complexes as Mammalian TrxR Inhibitors
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Is redox signaling a feasible target for overcoming multidrug resistance in cancer chemotherapy?
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Small molecules regulating reactive oxygen species homeostasis for cancer therapy
Zhang, J., Duan, D., Song, Z., Liu, T., Hou, Y., & Fang, J. (2021) · Medicinal Research Reviews · doi:10.1002/med.21734 · Cited by 184 · see citing works
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- Authors
- Zhang, J., Li, X., Han, X., Liu, R., & Fang, J.
- Affiliations
- State Key Laboratory of Applied Organic Chemistry (CN)
- Corresponding author
- Fang, Jianguo
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 38
- Issue
- 9
- Pages
- 794-808
- ISSN
- 0165-6147 (ISSN-L)
- OpenAlex
- W2709224048
- Cited by
- 460
- References
- 120
- Citations by year
- 2026: 38 · 2025: 55 · 2024: 55 · 2023: 66 · 2022: 61 · 2021: 61 · 2020: 45 · 2019: 47 · 2018: 28 · 2017: 3
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Lanzhou University Institutional Repository (submittedVersion)
- Funders
- Natural Science Foundation (21572093)
- Fundamental Research Funds (lzujbky-2016-49)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- thioredoxin, thioredoxin reductase, redox signaling, cancer therapy, small molecule inhibitors, anticancer agents, carcinogenesis, selective targeting
- MeSH terms
- Animals, Antineoplastic Agents, Enzyme Inhibitors, Humans, Neoplasms, Oxidation-Reduction, Structure-Activity Relationship, Thioredoxins, Thioredoxin-Disulfide Reductase, Small Molecule Libraries, Molecular Targeted Therapy
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