# Metabolic Constraints on Cancer Cell Proliferation

> **NIH NIH R00** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $42,419

## Abstract

Project Summary/Abstract
Cancers display altered cellular metabolism compared to the normal tissues from which they arise. One
promising therapeutic approach is to take advantage of these differences by designing interventions that target
the metabolic requirements of cancer cells. We have observed that maintaining aspartate levels is critical for
cancer cell proliferation by supporting the synthesis of the nucleotides and protein needed for proliferation. Our
work in tumor models has also indicated that intracellular aspartate is an endogenous metabolic limitation of
tumor growth. Aspartate is relatively impermeable to cells and must be synthesized from other metabolic
precursors. Thus, inhibiting the mechanisms cancer cells use to maintain aspartate levels is a potential method
of treating cancer. This proposal uses several approaches to target aspartate levels and determine the cancers
in which aspartate is most limiting. Specifically, we will determine the conditions in which aspartate is an
endogenous metabolic limitation for tumors (Aim 1), investigate if reductive glutamine metabolism supports
aspartate production in hypoxic cells (Aim 2), and test if altering asparagine synthesis can affect aspartate
levels and cancer cell proliferation (Aim 3). We will use cell culture to test the mechanistic elements of these
hypotheses and use preclinical mouse models of cancer to determine their efficacy in vivo. Together, these
studies will investigate new therapeutic methods to target the metabolism of cancer cells and to identify the
situations in which they are best deployed. The long-term scientific goal of this project is therefore to improve
cancer therapy by identifying new therapeutic targets and validating them in mouse models of cancer.

## Key facts

- **NIH application ID:** 10063706
- **Project number:** 3R00CA218679-03S1
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Lucas Bryan Sullivan
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $42,419
- **Award type:** 3
- **Project period:** 2020-07-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063706

## Citation

> US National Institutes of Health, RePORTER application 10063706, Metabolic Constraints on Cancer Cell Proliferation (3R00CA218679-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10063706. Licensed CC0.

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