Drug resistance in cancer: An overview
Open accessAbstract
Cancers have the ability to develop resistance to traditional therapies, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. This paper outlines the current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and the epithelial-mesenchymal transition, as well as how inherent tumor cell heterogeneity plays a role in drug resistance. It also describes the epigenetic modifications that can induce drug resistance and considers how such epigenetic factors may contribute to the development of cancer progenitor cells, which are not killed by conventional cancer therapies. Lastly, this review concludes with a discussion on the best treatment options for existing drug resistant cancers, ways to prevent the formation of drug resistant cancers and cancer progenitor cells, and future directions of study.
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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 [124]
Section 3 (page unavailable) says cancer progenitor cells, also called cancer stem cells, are often drug resistant and identifies increased MDR1 expression as one possible mechanism. Sections 2.4 and 2.5 discuss DNA repair and anti-apoptotic proteins as resistance mechanisms in cancers generally, but do not establish them as mechanisms specifically in cancer stem cells. The copy also does not establish altered drug-metabolism-associated markers as a cancer stem cell mechanism. (LLM, conf=0.88)
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Cited by
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- Authors
- Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., & Sarkar, S.
- Affiliations
- Arizona State University (US)
- Boston University (US)
- Harvard University (US)
- Corresponding author
- Sarkar, Sibaji
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2014-09-05
- Volume
- 6
- Issue
- 3
- Pages
- 1769-1792
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC4190567
- OpenAlex
- W2131487381
- Cited by
- 2,463
- References
- 112
- Citations by year
- 2026: 89 · 2025: 192 · 2024: 273 · 2023: 308 · 2022: 278 · 2021: 301 · 2020: 290 · 2019: 303 · 2018: 227 · 2017: 119 · 2016: 47 · 2015: 31 · 2014: 3
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Arizona State University Library Digital Repository (Arizona State University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- chemoresistance, drug inactivation, drug target alterations, drug efflux, DNA repair, cell death inhibition, epithelial-mesenchymal transition, tumor heterogeneity, epigenetic modifications, cancer stem cells
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