# Hyperthermic Intraperitoneal Chemotherapy Mechanisms in Epithelial Ovarian Cancer

> **NIH NIH R21** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $225,803

## Abstract

Project Summary
Epithelial ovarian cancer (EOC) is a leading cause of gynecologic cancer death in women, highlighting the critical
clinical need for new therapeutic strategies. In 2018 approximately 22,000 women were diagnosed with EOC in
the United States and the majority of them will ultimately succumb to their disease. The reason underlying the
poor survival is due to poor diagnosis with 80% of patients with EOC present in advanced stage (III-IV)
accounting for the poor prognosis (5-year cancer-specific survival 42% and 26%, respectively). Hyperthermic
intraperitoneal chemotherapy (HIPEC) has recently emerged as a clinical regimen that prolongs overall survival
for patients with advanced EOC by over 12 months compared to standard of care. Despite its proven clinical
benefit, how HIPEC extends survival remains poorly understood. Is the improvement in tumor control driven by
increased cytotoxic effects or alterations in the tumor microenvironment? What role does the immune system
play? To overcome this limitation, we analyzed ovarian tumors at the time of the debulking surgery and
immediately following HIPEC protocol. As EOC is often found to metastasize to the omental fat, we focused on
this site to interrogate cellular and molecular changes. We leveraged single cell RNA sequencing to identify the
major populations in the omental tumors and underlying cellular and molecular changes accompanying HIPEC.
Our data demonstrated that HIPEC activates immune cells and modulates the transcriptome of epithelial and
stromal cell populations. In parallel, we used a mouse EOC lines to develop an innovative hyperthermic
chemotherapy model. We determined that hyperthermic chemotherapy leads to increased immune cell infiltration
with a corresponding decrease in immune suppressor cells. Based on these observations, we hypothesize that
the survival benefit conferred by HIPEC is due to its ability to augment immune cell infiltration. We will test this
hypothesis using a complementary combination with an innovative mouse model of HIPEC and single cell
analysis of human patient specimen studies. We propose two Specific Aims. In Aim 1, we will test the
hypothesis that HIPEC promotes transcriptional activation of adaptive immune system. In Aim 2, we will test
hypothesis that HIPEC via attenuation of immune suppression improves EOC. The goal of the study is to gain
valuable information into the cellular pathways that HIPEC uses to disrupt EOC progression in order to translate
these findings into adjunct therapies to further enhance the clinical benefit of HIPEC for patients with
advanced EOC.

## Key facts

- **NIH application ID:** 10285567
- **Project number:** 1R21CA262984-01
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Ofer Reizes
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,803
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285567

## Citation

> US National Institutes of Health, RePORTER application 10285567, Hyperthermic Intraperitoneal Chemotherapy Mechanisms in Epithelial Ovarian Cancer (1R21CA262984-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10285567. Licensed CC0.

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