Chemical approaches to targeting drug resistance in cancer stem cells
Abstract
Cancer stem cells (CSCs) are a subpopulation of cancer cells with high clonogenic capacity and ability to reform parental tumors upon transplantation. Resistance to therapy has been shown for several types of CSC and, therefore, they have been proposed as the cause of tumor relapse. Consequently, much effort has been made to design molecules that can target CSCs specifically and sensitize them to therapy. In this review, we summarize the mechanisms underlying CSC resistance, the potential biological targets to overcome resistance and the chemical compounds showing activity against different types of CSC. The chemical compounds discussed here have been divided according to their origin: natural, natural-derived and synthetic compounds.
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Cancer stem cells exhibit intrinsic resistance to chemotherapy via overexpression of ATP-binding cassette (ABC) drug transporters, enhanced DNA repair capabilities, upregulation of anti-apoptotic proteins, and altered expression of drug metabolism-associated markers.
“CSCs, in particular, exhibit intrinsic resistance to chemotherapy via overexpression of ATP-binding cassette (ABC) drug transporters, enhanced DNA repair capabilities, upregulation of anti-apoptotic proteins, and altered expression of drug metabolism-associated markers [122,123,124].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [123]
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References 175 · Cited by 100
- Authors
- Sotiropoulou, P. A., Christodoulou, M. S., Silvani, A., Herold-Mende, C., & Passarella, D.
- Affiliations
- Université Libre de Bruxelles (BE)
- University of Milan (IT)
- Corresponding author
- Passarella, Daniele
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 19
- Issue
- 10
- Pages
- 1547-1562
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W2006460892
- Cited by
- 100
- References
- 175
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 10 · 2020: 8 · 2019: 5 · 2018: 14 · 2017: 13 · 2016: 18 · 2015: 13 · 2014: 2
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- cancer stem cells, drug resistance, chemosensitization, tumor recurrence, natural compounds, synthetic compounds, anticancer agents, therapeutic target
- MeSH terms
- Animals, Antineoplastic Agents, DNA Damage, DNA Repair, Humans, Neoplasms, Neoplastic Stem Cells, Apoptosis, Drug Resistance, Neoplasm
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