The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
A current perspective on the oncopreventive and oncolytic properties of selective serotonin reuptake inhibitors
Abstract
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers. In the current work, we discuss how the secondary mechanisms of action associated with these drugs mediate their oncolytic effect. In particular, sertraline limits tumor growth by abrogating the PI3K/akt signaling pathway, a growth pathway shown to be constitutively active in multiple cancers. Fluoxetine has been shown to activate the AMPA-type glutamate receptor, induce massive calcium influx and mitochondrial calcium overload and induce caspase-9-dependent apoptosis. This receptor being highly overexpressed in cancer stem cells may explain why SSRIs lower the risk of multiple types of cancer. Fluoxetine has also been shown to inhibit multidrug resistance pumps, increasing the efficacy of several standard chemotherapies. Given the vast potential of SSRIs in treating cancer, these drugs should be more heavily used not only in treating cancer-related depression, but in combating cancer and increasing the efficacy of standard of care chemotherapies.
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“Notably, the involvement of these proteins in tumour development might be related to the role of AMPAR in tumours (Radin and Patel 2017; Wang et al. 2020), together with the inflammatory function of NPTXs.”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Radin and Patel 2017
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Cites
Ca2+-Permeable AMPA Receptors Regulate Growth of Human Glioblastoma via Akt Activation
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Breast cancer recurrence risk related to concurrent use of SSRI antidepressants and tamoxifen
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Cited by
Gómez de San José, N., Massa, F., Halbgebauer, S., Oeckl, P., Steinacker, P., & Otto, M. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-021-02411-2 · Cited by 112
The Basic Characteristics of the Pentraxin Family and Their Functions in Tumor Progression
Wang, Z., Wang, X., Zou, H., Dai, Z., Feng, S., Zhang, M., Xiao, G., Liu, Z., & Cheng, Q. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01757 · Cited by 73
Metadata
- Authors
- Radin, D. P., & Patel, P.
- Affiliations
- University of Rochester (US)
- New York University (US)
- Corresponding author
- Radin, Daniel P.
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 87
- Pages
- 636-639
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W2573086553
- Cited by
- 32
- References
- 33
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 1
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- selective serotonin reuptake inhibitors, drug repurposing, oncolytic effect, cancer prevention, sertraline, fluoxetine, PI3K/Akt signaling, AMPA receptors, mitochondrial calcium overload, cancer stem cells, multidrug resistance pumps, chemotherapy efficacy, cancer-related depression
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Neoplasms, Neoplastic Stem Cells, Signal Transduction, Selective Serotonin Reuptake Inhibitors
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