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Article

The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells

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Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA
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Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA 02115, USA
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Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
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Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
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Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA
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Author to whom correspondence should be addressed.
Cancers 2019, 11(11), 1678; https://doi.org/10.3390/cancers11111678
Received: 24 September 2019 / Revised: 18 October 2019 / Accepted: 23 October 2019 / Published: 29 October 2019
(This article belongs to the Special Issue Cancer Stem Cells and Personalized Medicine for Gynecologic Cancers)
One of the most significant therapeutic challenges in the treatment of ovarian cancer is the development of recurrent platinum-resistant disease. Cancer stem cells (CSCs) are postulated to contribute to recurrent and platinum-resistant ovarian cancer (OvCa). Drugs that selectively target CSCs may augment the standard of care cytotoxics and have the potential to prevent and/or delay recurrence. Increased reliance on metabolic pathway modulation in CSCs relative to non-CSCs offers a possible therapeutic opportunity. We demonstrate that treatment with the metabolic inhibitor CPI-613 (devimistat, an inhibitor of tricarboxylic acid (TCA) cycle) in vitro decreases CD133+ and CD117+ cell frequency relative to untreated OvCa cells, with negligible impact on non-CSC cell viability. Additionally, sphere-forming capacity and tumorigenicity in vivo are reduced in the CPI-613 treated cells. Collectively, these results suggest that treatment with CPI-613 negatively impacts the ovarian CSC population. Furthermore, CPI-613 impeded the unintended enrichment of CSC following olaparib or carboplatin/paclitaxel treatment. Collectively, our results suggest that CPI-613 preferentially targets ovarian CSCs and could be a candidate to augment current treatment strategies to extend either progression-free or overall survival of OvCa. View Full-Text
Keywords: cancer stem cells (CSCs); ovarian cancer chemoresistance; metabolic inhibitor; combinational therapy cancer stem cells (CSCs); ovarian cancer chemoresistance; metabolic inhibitor; combinational therapy
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MDPI and ACS Style

Bellio, C.; DiGloria, C.; Spriggs, D.R.; Foster, R.; Growdon, W.B.; Rueda, B.R. The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells. Cancers 2019, 11, 1678. https://doi.org/10.3390/cancers11111678

AMA Style

Bellio C, DiGloria C, Spriggs DR, Foster R, Growdon WB, Rueda BR. The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells. Cancers. 2019; 11(11):1678. https://doi.org/10.3390/cancers11111678

Chicago/Turabian Style

Bellio, Chiara, Celeste DiGloria, David R. Spriggs, Rosemary Foster, Whitfield B. Growdon, and Bo R. Rueda. 2019. "The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells" Cancers 11, no. 11: 1678. https://doi.org/10.3390/cancers11111678

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