# Targeting Lipid Unsaturation in Ovarian Cancer Stem Cells

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $533,761

## Abstract

The focus of this multi-PI R01 application is to characterize and target a new metabolic vulnerability of ovarian
cancer stem cells (CSCs) discovered by our collaborative team. By using hyperspectral-stimulated Raman
scattering (SRS) imaging of single living cells and mass spectrometry analysis of extracted lipids we identified
increased levels of unsaturated fatty acids (UFAs) in ovarian CSCs compared to non-CSCs. We demonstrated
that UFAs are critical to the survival, proliferation, and tumorigenicity of ovarian CSCs. Here we propose to
analyze the mechanisms by which increased lipid unsaturation mediated by Δ9 desaturase (stearoyl-coA
desaturase, SCD1) regulates retinoic acid signaling in ovarian CSCs to determine cellular fate and promote
tumorigenicity. We will analyze whether the balance between saturated and unsaturated lipids enhance the
survival of drug-tolerant cells after chemotherapy. We will use SCD1 knock down and chemical inhibitors to
eradicate drug-tolerant cells persisting after treatment with platinum in ovarian xenografts and patient derived
xenografts (PDX). Lipid unsaturation will be visualized in CSCs in situ by using a multimodal high-speed SRS
microscope. Label-free molecular imaging will quantify CSCs and unsaturated lipids in human tumors and
xenografts before and after treatment with platinum or desaturase inhibitors. Ultimately, in depth
characterization of fatty acid metabolism in CSCs will reveal key pathways linked to stemness and persistence
of chemotherapy-tolerant cells. In the long run, our studies will develop new strategies to attack deadly ovarian
cancer.

## Key facts

- **NIH application ID:** 10241995
- **Project number:** 5R01CA224275-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ji-Xin Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $533,761
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241995

## Citation

> US National Institutes of Health, RePORTER application 10241995, Targeting Lipid Unsaturation in Ovarian Cancer Stem Cells (5R01CA224275-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241995. Licensed CC0.

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