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Phenotypic screenin...
Phenotypic screening platform identifies statins as enhancers of immune cell-induced cancer cell death.
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- Selvin, Tove (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Jarvius, Malin (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin,Science for Life Laboratory, SciLifeLab,Institutionen för farmaceutisk biovetenskap
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- Berglund, Malin (författare)
- Uppsala universitet,Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för biomaterialvetenskap,Institute of Clinical Sciences, Department of Biomaterials,Cancerfarmakologi och beräkningsmedicin
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- Lenhammar, Lena (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Nygren, Peter (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Rudbecklaboratoriet
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- Fryknäs, Mårten (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Larsson, Rolf (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Andersson, Claes (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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(creator_code:org_t)
- 2023-02-17
- 2023
- Engelska.
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 23:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- High-throughput screening (HTS) of small molecule drug libraries has greatly facilitated the discovery of new cancer drugs. However, most phenotypic screening platforms used in the field of oncology are based solely on cancer cell populations and do not allow for the identification of immunomodulatory agents.We developed a phenotypic screening platform based on a miniaturized co-culture system with human colorectal cancer- and immune cells, providing a model that recapitulates part of the tumor immune microenvironment (TIME) complexity while simultaneously being compatible with a simple image-based readout. Using this platform, we screened 1,280 small molecule drugs, all approved by the Food and Drug Administration (FDA), and identified statins as enhancers of immune cell-induced cancer cell death.The lipophilic statin pitavastatin had the most potent anti-cancer effect. Further analysis demonstrated that pitavastatin treatment induced a pro-inflammatory cytokine profile as well as an overall pro-inflammatory gene expression profile in our tumor-immune model.Our study provides an in vitro phenotypic screening approach for the identification of immunomodulatory agents and thus addresses a critical gap in the field of immuno-oncology. Our pilot screen identified statins, a drug family gaining increasing interest as repurposing candidates for cancer treatment, as enhancers of immune cell-induced cancer cell death. We speculate that the clinical benefits described for cancer patients receiving statins are not simply caused by a direct effect on the cancer cells but rather are dependent on the combined effect exerted on both cancer and immune cells.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomaterialvetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomaterials Science (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- pharmacology
- Immunomodulating Agents
- Early Detection of Cancer
- High-Throughput Screening Assays
- Small Molecule Libraries
- pharmacology
- Neoplasms
- drug therapy
- genetics
- Cell Death
- Tumor Microenvironment
- Immuno-oncology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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