# Investigating the Metabolic Reprogramming of Ovarian Tumors During Omental Metastasis

> **NIH NIH F30** · DUKE UNIVERSITY · 2022 · $37,016

## Abstract

ABSTRACT
Ovarian cancer (OC) is the most lethal gynecological malignancy, with
aggressive metastatic disease responsible for the majority of ovarian cancer related
deaths. Despite the clinical significance of OC omental metastases, the precise
molecular mechanisms which drive this phenomenon have not been well characterized,
making the resulting aggressive phenotype even more puzzling. The long-term goal of
this project is develop a more comprehensive understanding of the metabolic factors
which allow ovarian cancer cells to colonize and proliferate at metastatic sites within the
omentum. One aspect we are particularly interested in is the role of the pentose
phosphate pathway (PPP), a metabolic pathway responsible for producing nucleotide
pentose precursors through a nonoxidative series of reactions and the reducing
equivalent NADPH through a distinct oxidative branch. We believe this pathway may
contribute to metastatic potential and proliferation. Building on recent evidence
demonstrating that ovarian cancer cells undergo metabolic reprogramming to adapt to
the unique, lipid rich omentum environment, we also believe that increased PPP is
adapted by metastasizing cells as a compensatory mechanism.
Thus the overall aim of this project is characterize changes in the PPP which are
relevant for omental metastases, during which cancer cells must both adjust to a new
microenvironmental niche and proliferate rapidly. The central hypothesis of this
proposal is that the generation of reducing equivalents and nucleotide precursors via
the PPP meets the proliferative demands and maintains the redox homeostasis required
for omental metastasis. To determine if nucleotide precursor synthesis via the PPP
promotes proliferation, I will interrogate the importance the oxidative branch using in
vitro and in vivo models on omental metastasis in Aim 1. In Aim 2, I will use live-cell
intravital imaging of the omentum coupled with genetically-expressed biosensors to
define the redox requirements of metastatic colonization. This proposed research will
allow us to advance our collective understanding of the metabolic landscape present in
ovarian tumors and the precise manner in which metabolic reprogramming promotes
metastasis. These insights may open therapeutic avenues to target metabolic
vulnerabilities.

## Key facts

- **NIH application ID:** 10328248
- **Project number:** 5F30CA257365-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Shree Bose
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $37,016
- **Award type:** 5
- **Project period:** 2021-06-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328248

## Citation

> US National Institutes of Health, RePORTER application 10328248, Investigating the Metabolic Reprogramming of Ovarian Tumors During Omental Metastasis (5F30CA257365-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328248. Licensed CC0.

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