# Multi-omic Predictive Markers for Ovarian Cancer Therapy Response and Outcomes

> **NIH NIH R21** · MAGEE-WOMEN'S RES INST AND FOUNDATION · 2022 · $261,420

## Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with more than 20,000 
newly- diagnosed cases and over 13,000 deaths in the United States each year. Unfortunately, there 
has been little change in survival since platinum-based therapies were introduced over 30 years 
ago. Because the search for newer, more effective agents has not been fruitful, aggressive surgery 
plus platinum-based chemotherapy remains the standard first-line treatment of the disease. However, 
individual response to platinum therapy is highly variable and unpredictable. Eventually, most 
women develop and succumb to platinum-resistant disease. No way exists to identify who will respond 
poorly to platinum-based therapy; nor are there any clinically-validated interventions to improve 
therapy response. Biomarkers that can predict therapy response, provide an early indication of 
efficacy, support patient treatment stratification, and suggest interventions to improve therapy 
response and survival are urgently needed. Basic cancer research discoveries in EOC and other solid 
tumors suggest that gut bacteria impact how a woman responds to platinum-based therapy by 
influencing the local tumor microenvironment (TME). Thus, gut  bacteria may serve as predictive 
biomarkers of therapy response and outcome. However, there have been no human studies of gut 
bacteria and EOC therapy response, nor on the interactions among gut bacteria, TME immunity, and 
treatment response and outcome.
Our preliminary findings in women with newly-diagnosed EOC support the animal model data. Backed by 
the laboratory research data and based on our preliminary findings in an EOC population, we propose 
to develop predictive microbiome-based biomarkers that will lead to better patient stratification. 
In Aim 1, we will assess the gut microbiome and systemic metabolome in 104 newly diagnosed EOC 
cases to identify gut bacteria predictive of response and outcome to platinum-based therapy. In Aim 
2 we will use immune-profiling assays to assess TME immune infiltrates and immune gene expression 
in our cohort. We will then use the high- dimensional genomic, metabolomic and transcriptomic data 
generated from Aims 1 and 2 to identify favorable and unfavorable gut microbiomes associated with 
therapy response, outcomes, and local tumor immunity. We will also identify gut bacteria that can 
serve as intervention targets to improve therapy efficacy or block cancer progression. Our team 
will then be well positioned to conduct human trials to assess the effects of altering gut bacteria 
composition on EOC outcomes. We will also be well positioned to pursue mechanistic studies to 
illuminate how gut bacteria impact therapy response and outcome, thus further identifying treatment 
targets. This proposal uses existing biospecimens from previously-funded NCI projects together with 
clinical annotating data to generate high-dimensional, multi-omic data in order to develop 
predictive and pro...

## Key facts

- **NIH application ID:** 10351697
- **Project number:** 1R21CA267050-01
- **Recipient organization:** MAGEE-WOMEN'S RES INST AND FOUNDATION
- **Principal Investigator:** FRANCESMARY MODUGNO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $261,420
- **Award type:** 1
- **Project period:** 2022-08-08 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10351697

## Citation

> US National Institutes of Health, RePORTER application 10351697, Multi-omic Predictive Markers for Ovarian Cancer Therapy Response and Outcomes (1R21CA267050-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10351697. Licensed CC0.

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