# Glycine metabolism in cancer

> **NIH NIH R00** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $324,297

## Abstract

Project Summary
 Cancer cells have a distinct metabolism that supports their pathological
proliferation. Targeting this metabolism has led to many of the existing chemotherapies
in the clinic today such as antifolates. The amino acid glycine is primarily produced by
folate metabolism, a pathway that is nearly universally upregulated in cancer. Glycine
supports important biosynthetic processes including protein, purine and glutathione
synthesis. In addition, glycine catabolic processes have recently been shown to be
important in cancer stem cells and glioblastoma. In newly published data, I
demonstrated that glycine-supported antioxidant production is crucial for cancer cell
growth. This proposal seeks to quantitatively characterize glycine metabolism in cancer
and to test the hypothesis that folate-mediated glycine synthesis supports glutathione
production and thus redox homeostasis. In these efforts, I will benefit from a new small
molecule that I discovered, which potently inhibits both isozymes of the glycine synthetic
enzyme SHMT. In Aim 1, I will use isotope tracers to quantitate glycine production and
consumption fluxes in normal and cancer cells, and apply these findings in vivo. In Aim
2, I will further develop the SHMT inhibitor and test it in a mouse model of B-cell
lymphoma, a tumor type that is defective in glycine import and accordingly highly
sensitive SHMT inhibition in vitro. Collectively, these experiments will lay the groundwork
for targeting of glycine metabolism as a new therapeutic approach in cancer. Under the
guidance of my primary mentor and my team of collaborators during the K99 period, this
proposal will allow me to successfully transition from my current mentored position into a
independent research group leader.

## Key facts

- **NIH application ID:** 10055956
- **Project number:** 5R00CA215307-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Gregory S Ducker
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $324,297
- **Award type:** 5
- **Project period:** 2018-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055956

## Citation

> US National Institutes of Health, RePORTER application 10055956, Glycine metabolism in cancer (5R00CA215307-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10055956. Licensed CC0.

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