# Using dietary glutamine supplementation for melanoma prevention and targeted therapy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $410,444

## Abstract

PROJECT SUMMARY
 Despite recent advances in cancer metabolism, whether and how nutritional interventions affect tumor
development, metastasis and therapeutic response are still poorly understood. Thus, the goal of this study is to
elucidate the effect of glutamine supplementation on tumor development and therapeutic responses, and
eventually provide molecular evidence that nutritional interventions on cancer patients can inhibit tumor growth
and sensitize tumors to treatments. Using metabolomic analysis, we and others have found that, compared to
other amino acids, many solid tumor cells are situated in a glutamine poor environment in vivo. Interestingly, we
found that glutamine deficiency in melanoma tumors resulted in cancer cell de-differentiation and resistance to
treatment due to increased histone methylation levels. This finding further prompted us to test if increases in
glutamine levels through dietary supplementation can be detrimental to tumor cells that have been well adapted
to a low glutamine environment. Our preliminary data demonstrated that supplementation of glutamine in the diet
is sufficient to increase tumoral α-ketoglutarate levels and leads to decreased histone methylation in melanoma
patient-derived xenograft (PDX) tumors. Importantly, we found that high glutamine diet significantly hinders tumor
growth and decreases expression of melanoma-associated oncogenes compared to control diet. In support with
this, accumulating evidence from in vivo experiments demonstrate that glutamine is not an essential nutritional
source to support TCA cycle and tumor growth. Thus, we hypothesize that dietary glutamine supplementation
inhibits melanoma tumor growth and sensitizes tumor cells to current treatments via epigenetic reprogramming.
In this proposal, we will 1) determine the effect of dietary glutamine supplementation on melanoma tumor growth,
metabolism and oncogene expression in vivo; 2) determine the molecular mechanisms by which glutamine
supplementation inhibits tumor growth; 3) investigate the effect of glutamine supplementation in response to
BRAF/MEK inhibitors and immunotherapy for melanoma treatment. Despite many proven clinical benefits of
glutamine supplementation to cancer patients, recent in vitro studies showing that tumor cells are avid glutamine
consumers led to cautionary usage of dietary glutamine on cancer patients. Completion of the proposed studies
will provide insight into glutamine driven epigenetic regulation and its effect on tumor growth. The results of these
studies will reveal a novel therapeutic direction for using dietary glutamine supplementation to prevent tumor
growth and enhance therapeutic responses without detrimental side effects.

## Key facts

- **NIH application ID:** 10657330
- **Project number:** 5R01CA244360-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** MEI KONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $410,444
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10657330

## Citation

> US National Institutes of Health, RePORTER application 10657330, Using dietary glutamine supplementation for melanoma prevention and targeted therapy (5R01CA244360-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10657330. Licensed CC0.

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