An overview of the past decade of bufalin in the treatment of refractory and drug-resistant cancers: current status, challenges, and future perspectives
Open accessAbstract
Profound progress has been made in cancer treatment in the past three decades. However, drug resistance remains prevalent and a critical challenge. Drug resistance can be attributed to oncogenes mutations, activated defensive mechanisms, ATP-bind cassette transporters overexpression, cancer stem cells, etc. Chinese traditional medicine toad venom has been used for centuries for different diseases, including resistant cancers. Bufalin is one of the bufadienolides in toad venom that has been extensively studied for its potential in refractory and drug-resistant cancer treatments in vitro and in vivo. In this work, we would like to critically review the progress made in the past decade (2013–2022) of bufalin in overcoming drug resistance in cancers. Generally, bufalin shows high potential in killing certain refractory and resistant cancer cells via multiple mechanisms. More importantly, bufalin can work as a chemo-sensitizer that enhances the sensitivity of certain conventional and targeted therapies at low concentrations. In addition, the development of bufalin derivatives was also briefly summarized and discussed. We also analyzed the obstacles and challenges and provided possible solutions for future perspectives. We hope that the collective information may help evoke more effort for more in-depth studies and evaluation of bufalin in both lab and possible clinical trials.
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Bufalin has emerged as a clinically validated natural compound with therapeutic potential across multiple cancer types.
“Bufalin has emerged as a clinically validated natural compound with therapeutic potential across multiple cancer types.”
From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [37]
The Introduction describes bufalin as a natural compound with anticancer potential across multiple cancer types. It does not establish that bufalin is clinically validated: the Introduction says a phase II pancreatic-cancer trial posted no results, and the Discussion calls for further animal testing before clinical trials. (LLM, conf=0.91)
Experimental — accuracy not yet measuredMechanistic studies reveal Bufalin's pleiotropic anti-tumor effects through cancer-type-specific targets.
“Mechanistic studies reveal its pleiotropic anti-tumor effects through cancer-type-specific targets5,37.”
From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [37]
The Discussion’s summary describes bufalin as a multi-targeting or multi-functional agent with several anticancer mechanisms. But the Future perspectives section says it remains unknown how its targets work together and whether its cytotoxicity is cancer-type-dependent; the review does not establish that the targets are cancer-type-specific. (LLM, conf=0.84)
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- Authors
- Ye, Q., Zhou, X., Ren, H., Han, F., Lin, R., & Li, J.
- Affiliations
- Hainan Normal University (CN)
- Hainan Medical University (CN)
- Hainan General Hospital (CN)
- Hubei University of Chinese Medicine (CN)
- Corresponding author
- Ye, Qingmei
- Li, Juan
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2023-10-04
- Volume
- 14
- Pages
- 1274336-1274336
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC10582727
- OpenAlex
- W4387335716
- Cited by
- 15
- References
- 155
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China
- Topics
- Physical Sciences › Materials Science › Biomaterials › Phytochemistry and Bioactive Compounds
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Plant-based Medicinal Research
- Keywords
- bufalin, bufadienolides, toad venom, drug-resistant cancer, refractory cancer, chemosensitization, ABC transporters, cancer stem cells, anticancer mechanism
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