# Role of Age-Related Changes in the Tumor Microenvironment on Ovarian Cancer Progression

> **NIH NIH R03** · DUKE UNIVERSITY · 2021 · $80,500

## Abstract

Project Summary/Abstract
Epithelial ovarian cancer (EOC) is the deadliest gynecologic disease that is most commonly diagnosed in women
postmenopausal, aged 55-64 years (median, 63). Although survival of patients with EOC has shown some improvement
over the past three decades for younger women, the same is not true for older patients. Two major factors that impact
prognosis and survival are metastasis and recurrence, and these are known to be positively related to aging. The
mechanisms that underlie the influence of age on ovarian cancer development, progression and recurrence are poorly
defined. We will use a xenograft rat model of EOC to help fill these gaps in knowledge and define how aging impacts
EOC development and progression. Based on limited prior studies, we hypothesize that the gene regulation pathways and
metabolic modification of aged versus younger tumor microenvironment (TME) – with a focus on the ECM – contribute
to a more aggressive ovarian cancer phenotype. Our specific aims are: 1) to determine gene expression and cellular
metabolic profiles of abdominal fat tissues from young and aged (estropause) rats; and 2) to determine gene expression
and cellular metabolic profiles of ovarian cancer stroma tissues. The longitudinal study design will permit analysis
throughout the course of cancer development and progression with three targeted timepoints, including analysis prior to
cancer initiation, during cancer progression and at recurrence. Given the strong propensity for ovarian cancer cells to
embed and grow in omental fat, we will specifically focus attention on changes in this fat tissue TME during aging (and
estropause in rat) and over the course of disease. We will determine how metabolic and RNAseq gene expression profiles
differ between young and aged rats without malignancy and then examine how age-specific differences vary in the context
of cancer progression. Bioinformatic analyses will determine if there is enrichment of particular gene ontology terms and
pathways among the differentially expressed genes. We expect findings from this study will provide data to support a
larger study by revealing new targets to aid prevention of metastasis and/or recurrence which can be further evaluated in
preclinical models with the objective of translation to clinical trials for older and postmenopausal EOC patients.

## Key facts

- **NIH application ID:** 10302999
- **Project number:** 1R03AG068685-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Zhiqing Huang
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $80,500
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302999

## Citation

> US National Institutes of Health, RePORTER application 10302999, Role of Age-Related Changes in the Tumor Microenvironment on Ovarian Cancer Progression (1R03AG068685-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10302999. Licensed CC0.

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