Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions
Open accessAbstract
Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin ("old drugs") to their recently recognized CSC targets ("new uses") within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the "old drugs-new uses" repurposing strategy to open a new CSC-targeted chemoprevention era.
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Animal experiments have elucidated the mechanisms underlying these epidemiological findings, i.e., suppression of cancer stem cells.
“Animal experiments have elucidated the mechanisms underlying these epidemiological findings, i.e., suppression of cancer stem cells(264);”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [264]
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- Authors
- Vazquez-Martin, A., López-Bonetc, E., Cufí, S., Oliveras-Ferraros, C., Del Barco, S., Martin-Castillo, B., & Menendez, J. A.
- Affiliations
- Institut d'Investigació Biomèdica de Girona (ES)
- Institut Català d'Oncologia (ES)
- ORCID
- Cufí, Sílvia
- Venue
- Drug Resistance Updates
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 14
- Issue
- 4-5
- Pages
- 212-223
- ISSN
- 1368-7646 (ISSN-L)
- PMC
- PMC3742095
- OpenAlex
- W2007750854
- Cited by
- 66
- References
- 166
- Citations by year
- 2026: 1 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 10 · 2013: 8 · 2012: 9
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Drug Resistance Updates (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Fundación Científica Asociación Española Contra el Cáncer
- China Scholarship Council
- Ministerio de Ciencia e Innovación
- Instituto de Salud Carlos III
- National Cancer Institute (P30CA006973)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- drug repurposing, cancer stem cells, chloroquine, metformin, precancerous lesions, intraepithelial neoplasia, oncogene-induced senescence, signaling networks, chemoprevention, self-renewal, systems biology
- MeSH terms
- Aging, Animals, Antimalarials, Antineoplastic Agents, Autophagy, Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Chloroquine, Drug Evaluation, Preclinical, Female, Humans, Hypoglycemic Agents, Metformin, Neoplasms, Phenotype, Neoplastic Stem Cells, Signal Transduction, TGF-beta Superfamily Proteins, Drug Repositioning, Epithelial-Mesenchymal Transition, Molecular Targeted Therapy
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