# Targeting mitochondrial adaptations to suppress metastatic outgrowth in serous ovarian cancer

> **NIH NIH F31** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2021 · $35,494

## Abstract

PROJECT SUMMARY
Serous ovarian cancer is the 5th leading cause of cancer-related deaths in women, with a 30% survival rate when
spread into the highly hypoxic and visceral peritoneal cavity. Despite efforts to treat this highly metastatic
disease, traditional chemotherapeutic and cytoreductive therapies are unable to diminish or induce cell death of
circulating metastases from colonizing secondary sites due to their genetic and histologic heterogeneity. The
dissemination route for primary metastasis, however, is most often conserved to the peritoneal cavity, which is
low in nutrients and hypoxic (1-2% O2). Cells exfoliated from the primary tumor will aggregate during migration,
which elicits a survival signal to maintain viability in this environment. The underlying cellular and molecular
changes involved with aggregation has yet to be determined. We have previously found that aggregation of
murine ovarian surface epithelial (MOSE) cells present a more suppressed metabolic phenotype upon
aggregation accompanied by an increase in localized mitochondrial fragmentation. My proposed research seeks
to identify a phenotypic switch from enhanced mitophagy during peritoneal dissemination that supports survival
of ovarian cancer cell aggregates to mitochondrial biogenesis during secondary tissue colonization that enables
proliferation. I will use a syngeneic murine model of progressive ovarian cancer grown in physiologically relevant
conditions to characterize changes in mitochondrial dynamics during aggregation, adhesion and secondary
outgrowth. I then will use specific inhibitors to block the reversibility of these changes to confirm their relevance
for tumor outgrowth in vitro and in vivo. This proposed research will contribute to understanding the role of
mitophagy as a survival rather than apoptotic signal in cancer cells as adaptation to nutrient-deprived
environments, while also identifying how these processes can be reversed to support invasion and metastatic
capacity during secondary colonization. This proposal is significant because it will identify molecular adaptations
associated with the viability of disseminating cancer metastases as well as promote novel preventative
therapeutics that can be used to limit the mortality of highly aggressive ovarian cancer in women.

## Key facts

- **NIH application ID:** 10235618
- **Project number:** 1F31CA261146-01
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Joe Grieco
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $35,494
- **Award type:** 1
- **Project period:** 2021-07-10 → 2022-05-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235618

## Citation

> US National Institutes of Health, RePORTER application 10235618, Targeting mitochondrial adaptations to suppress metastatic outgrowth in serous ovarian cancer (1F31CA261146-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10235618. Licensed CC0.

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