# Interval exercise training as a therapy for endometrial cancer

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $168,381

## Abstract

PROJECT SUMMARY
 Obesity and diabetes are associated with increased risk of developing endometrial cancer (EC) and
increased risk of death. Obese EC patients have a 9-fold higher mortality from all causes compared with non-
obese patients. Thus, it seems logical that interventions to combat obesity, insulin resistance and
cardiometabolic health may improve EC outcomes. High-intensity interval training (HIIT) is a time-efficient
exercise strategy in which short intense exercise periods are interspersed with recovery periods. HIIT requires
as little as 10 minutes of exercise per session (2 times a wk) and rapidly improves cardiorespiratory fitness and
other metabolic outcomes in as few as 2 wks. In overweight/obese adults, we found that 3 wks of HIIT results in
significant improvements in markers of cardiovascular health, triglycerides, lipids and insulin. In addition, we
have demonstrated that HIIT is feasible in pre-bone marrow transplant patients, with 70% completing 6 wks of
training prior to transplant. Collectively, these preliminary data support the feasibility and applicability of HIIT in
obese EC patients.
 We have explored the chemotherapeutic potential of the anti-diabetic drug metformin in EC. In the
LKB1fl/flp53fl/fl EC mouse model, diet-induced obesity led to a doubling of tumor size and increases in lipid
biosynthesis. Metformin showed increased efficacy against EC in obese vs. lean mice and reversed the
detrimental metabolic effects of obesity in ECs. In our phase 0 clinical trial of obese EC patients, short-term
metformin treatment reduced proliferation and decreased expression of targets of the insulin/mTOR pathway
within the ECs. Metformin had beneficial effects on lipid pathways in responders to treatment. In a similar phase
0 clinical trial, we propose to assess HIIT as a metabolic treatment of EC.
 We hypothesize that HIIT will reduce tumor growth and improve the metabolic milieu of EC patients,
specifically through inhibition of insulin and lipid pathways. To explore this hypothesis, we will conduct a
randomized pre-operative HIIT intervention in obese EC patients. Women who undergo surgical staging for EC
will receive a 3-wk home-based HIIT exercise treatment versus standard of care (no HIIT intervention) that will
be completed twice weekly. The goal of this trial is to assess the impact of HIIT on EC proliferation and related
metabolic pathways by comparing pre-intervention endometrial biopsies to post-intervention hysterectomy
specimens. In parallel, we will delineate the interplay of HIIT on the cardiometabolic health of the EC patients
via a comprehensive assessment of cardiovascular and metabolic biomarkers of HIIT response that includes
traditional (VO2peak, BMI, HgBA1C, fasting insulin/glucose, lipids) and novel (metabolomic profiling) biomarkers.
This innovative approach will lead to a greater understanding of the feasibility and initial effects of HIIT in EC
treatment. This will be the first trial of HIIT in EC and ...

## Key facts

- **NIH application ID:** 9842815
- **Project number:** 5R21CA235029-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Victoria Lin Bae-Jump
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $168,381
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842815

## Citation

> US National Institutes of Health, RePORTER application 9842815, Interval exercise training as a therapy for endometrial cancer (5R21CA235029-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842815. Licensed CC0.

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