# Utilization of Fasting Mimicking Diets to Treat and Prevent Clear Cell Renal Cell Carcinoma

> **NIH NIH F99** · UNIVERSITY OF NOTRE DAME · 2022 · $48,252

## Abstract

Von Hippel Lindau (VHL) disease is a rare genetic disorder effecting 1 in 36,000 Americans every year with an
average life expectancy of 49 years. Currently, there is no long-term treatment for the spontaneous tumors that
patients develop across their body, markedly, kidneys in the form of Clear Cell Renal Cell Carcinoma (ccRCC).
With limited pharmacological treatments available dietary modifications have become a topic of interest for
several cancer types. Notably a ketogenic diet containing high fat (>80%) and low carbohydrate (<10%) alters
metabolism at the organ and cellular level to preferentially utilize fats and ketones for fuel. Recent data I have
generated suggests that two diets that generate the ketone beta-hydroxybutyrate (BHB); the Cyclical Ketogenic
Diet (CKD) and a diet containing pre-ketone 1,3 butanediol (BD), both shrink subcutaneous tumors in NCr Nude
mice from the human ccRCC cell line 7860. Furthermore, nude mice with orthotopic 7860 tumors who are fed a
CKD had a life expectancy 58% longer than those on a standard diet (SD). When mice were fed a CKD for two
weeks before orthotopic injections of 7860, 9/10 kidneys in CKD fed mice showed minimal tumor signal and
overall tumor growth was significantly lower than that of tumor growth in kidneys in SD fed mice, implying that a
CKD has significant prophylactic capabilities against ccRCC. In-vitro analysis of several human ccRCC cell lines
shows that BHB addition halts growth of these cells but does not significantly affect growth of non-cancerous
kidney cells. Furthermore, BHB addition to ccRCC cells shows significant changes in several key markers of
ferroptosis such as TFRC and SLC7A11 with BODIPY C11 and 4-hydroxynonenal (4-HN) being upregulated in
tumors as well as cells and halting growth in-vitro. It is important to note that VHL loss has recently been
associated with an increase sensitivity to ferroptosis. With these data in mind we hypothesize that BHB generated
from a CKD and BD alters gene expression and metabolic processes to induce ferroptosis in ccRCC cancer
cells. Also, that this mechanism could be generalized to several cancers associated with VHL mutations and
potentially be utilized as a prophylactic to prevent many tumors that arise in those with VHL disease. With these
data to be generated I hope to publish in high impact relevant journals such as Cancer Metabolism, apply for
additional federal funding, and establish this mechanism in more robust pre-clinical settings to lay the
groundwork to make real life impacts on patients.

## Key facts

- **NIH application ID:** 10529914
- **Project number:** 1F99CA274694-01
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Sean Andrew Murphy
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $48,252
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10529914

## Citation

> US National Institutes of Health, RePORTER application 10529914, Utilization of Fasting Mimicking Diets to Treat and Prevent Clear Cell Renal Cell Carcinoma (1F99CA274694-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10529914. Licensed CC0.

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