Mechanisms on chemotherapy resistance of colorectal cancer stem cells and research progress of reverse transformation: A mini-review
Open accessAbstract
Tumor recurrence and chemotherapy resistance are mainly responsible for poor prognosis in colorectal cancer (CRC) patients. Cancer stem cell (CSC) has been identified in many solid tumors, including CRC. Additionally, CSC cannot be completely killed during chemotherapy and develops resistance to chemotherapeutic drugs, which is the main reason for tumor recurrence. This study reviews the main mechanisms of CSC chemotherapy resistance in CRC, including activation of DNA damage checkpoints, epithelial-mesenchymal transition (EMT), inhibition of the overexpression of antiapoptotic regulatory factors, overexpression of ATP-binding cassette (ABC) transporters, maintenance of reactive oxygen species (ROS) levels, and the dormant state of CSC. Advances in research to reverse chemotherapy resistance are also discussed. Our study can provide the promising potential for eliminating CSC and preventing tumor progression for CRC treatment.
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Repurposed drugs like metformin and NSAIDs, as well as natural products such as curcumin, salvianolic acid, and vitamin C are being studied for their ability to target colorectal CSC self-renewal, proliferation, apoptosis, and ROS pathways and help overcome therapy resistance.
“Additionally, repurposed drugs like metformin and NSAIDs, as well as natural products such as curcumin, salvianolic acid, and vitamin C are being studied for their ability to target colorectal CSC self-renewal, proliferation, apoptosis, and ROS pathways and help overcome therapy resistance [148,210].”
From Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer (2025) · cites this paper as [210]
The Natural agents section (page unavailable) reports that curcumin and salvianolic acid B affect colorectal cancer stem cells and can help reverse chemotherapy resistance. The Maintenance of ROS levels section discusses vitamin C increasing intracellular ROS, but does not establish that it targets colorectal CSCs. Searches for metformin and NSAIDs found no discussion of either drug in our copy, and the paper does not link every listed agent to all four named pathways or processes. (LLM, conf=0.88)
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Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer
Haynes, J., & Manogaran, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26051988 · Cited by 82 · see citing works
“…repurposed drugs like metformin and NSAIDs, as well as natural products such as curcumin, salvianolic acid, and vitamin C are being studied for their ability to target colorectal CSC self-renewal, proliferation, apoptosis, and ROS pathways and help overcome therapy resistance [148,210].”
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Ye, Q., Zhou, X., Ren, H., Han, F., Lin, R., & Li, J. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1274336 · Cited by 15 · see citing works
- Authors
- Chen, L., Yang, F., Chen, S., & Tai, J.
- Affiliations
- First Hospital of Jilin University (CN)
- Corresponding author
- Tai, Jiandong
- Venue
- Frontiers in Medicine
- Publisher
- Frontiers Media SA
- Published
- 2022-09-12
- Volume
- 9
- Pages
- 995882-995882
- ISSN
- 2296-858X (ISSN-L)
- PMC
- PMC9510709
- OpenAlex
- W4296524786
- Cited by
- 60
- References
- 56
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 24 · 2023: 14
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Department of Finance of Jilin Province
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- colorectal cancer, cancer stem cells, chemoresistance, tumor recurrence, DNA damage checkpoint, epithelial-mesenchymal transition, anti-apoptotic factors, ABC transporters, reactive oxygen species, stem cell quiescence, drug resistance reversal
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