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Int J Mol Sci. 2019 Jan 8;20(1). pii: E229. doi: 10.3390/ijms20010229.

Targeting Mitochondria for Treatment of Chemoresistant Ovarian Cancer.

Author information

1
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota, Minneapolis, MN 55455, USA. edieb.543@gmail.com.
2
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota, Minneapolis, MN 55455, USA. smullany@umn.edu.
3
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota, Minneapolis, MN 55455, USA. zechang@umn.edu.
4
Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, VA 22908, USA. CL3NJ@hscmail.mcc.virginia.edu.
5
Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institute, S-171 76 Stockholm, Sweden. Stig.Linder@liu.se.
6
Department of Medical Health Sciences (IMH), Linköping University, S-751 85 Linköping, Sweden. Stig.Linder@liu.se.
7
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota, Minneapolis, MN 55455, USA. mbazzaro@umn.edu.

Abstract

Ovarian cancer is the leading cause of death from gynecologic malignancy in the Western world. This is due, in part, to the fact that despite standard treatment of surgery and platinum/paclitaxel most patients recur with ultimately chemoresistant disease. Ovarian cancer is a unique form of solid tumor that develops, metastasizes and recurs in the same space, the abdominal cavity, which becomes a unique microenvironment characterized by ascites, hypoxia and low glucose levels. It is under these conditions that cancer cells adapt and switch to mitochondrial respiration, which becomes crucial to their survival, and therefore an ideal metabolic target for chemoresistant ovarian cancer. Importantly, independent of microenvironmental factors, mitochondria spatial redistribution has been associated to both tumor metastasis and chemoresistance in ovarian cancer while specific sets of genetic mutations have been shown to cause aberrant dependence on mitochondrial pathways in the most aggressive ovarian cancer subtypes. In this review we summarize on targeting mitochondria for treatment of chemoresistant ovarian cancer and current state of understanding of the role of mitochondria respiration in ovarian cancer. We feel this is an important and timely topic given that ovarian cancer remains the deadliest of the gynecological diseases, and that the mitochondrial pathway has recently emerged as critical in sustaining solid tumor progression.

KEYWORDS:

OXPHOS; SWI/SNF complex; ascites; chemoresistant ovarian cancer; mitochondrial inhibitor

PMID:
30626133
DOI:
10.3390/ijms20010229
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