# Understanding Sex Disparities in Gliomas Through Sex Differences in Mitochondrial Activity

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $205,538

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Ippolito, Joseph Edward
PROJECT SUMMARY
 There is a sex disparity seen in cancers throughout the body where males have both a higher incidence and
a higher mortality than females. This is not only true for adults, but is also seen in children as well, suggesting
that factors other than the effects of sex hormones may be playing a role in this phenomenon. This is especially
true for glioblastomas (GBM) that comprise over 50% of brain tumors and are characterized by resistance to
therapies and a dismal prognosis (median survival - 15 months). Because enhanced nutrient consumption and
metabolism are critical to enhanced tumorigenesis and its effect on poor patient outcomes, our group
investigates the presence of sex differences in cancer metabolism that may be driving the sex disparities that
are observed in many cancers. We have uncovered laboratory and clinical evidence demonstrating that male
brain tumors have enhanced nutrient uptake and metabolism (specifically sugars and amino acids) compared to
female tumors. We have further identified that the largest sex differences in cancer metabolism come from the
mitochondria, the part of the cell that is the critical for generating energy and biosynthetic building blocks for the
cell for growth. Because metabolism is not only restricted to the tumor, but involves the entire patient, we have
investigated the effects of sex differences in nutrition and obesity in cancer patient survival. We have discovered
that women with “male-pattern” increased visceral abdominal obesity selectively do much worse compared to all
other patients in multiple cancers. These findings suggest that the sex differences that we see in cancers may
not only be related to tumor mitochondria, but nutrition and its overall metabolic health of the individual. In this
proposal, we will develop new animal models to test the hypothesis that sex differences in mitochondrial activity
underlie sex differences in tumor development. Our long term goal is to understand the metabolic basis of sex
disparities in cancer patients through a combination of tumor and host metabolism. In the first aim of this
proposal, we will use an established model (Nf1-/-/DNp53) for sex differences in GBM and deplete mitochondria
in the cancer cells to test for sex differences in cancer cell phenotype and metabolism. In the second aim, we
will determine the effects of obesogenic diets on sex differences in brain tumor mitochondrial activity and growth.
This research proposal is innovative because it opens up a new paradigm in the oncology field that investigates
sex-specific differences in cancer and host metabolism. This proposal will generate new insights into the
mechanism behind sex differences in mitochondrial activity and the impact of nutrition on sex differences in the
malignant phenotype. We are beginning to develop a platform for novel readily-translatable imaging methods
and therapeutic app...

## Key facts

- **NIH application ID:** 9994966
- **Project number:** 5R21CA242221-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Joseph Edward Ippolito
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $205,538
- **Award type:** 5
- **Project period:** 2019-08-13 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994966

## Citation

> US National Institutes of Health, RePORTER application 9994966, Understanding Sex Disparities in Gliomas Through Sex Differences in Mitochondrial Activity (5R21CA242221-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9994966. Licensed CC0.

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