# Metabolic Constraints on Cancer Cell Proliferation

> **NIH NIH R00** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $223,720

## 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 recently observed that maintaining aspartate levels is
critical for cancer cell proliferation by supporting the synthesis of the nucleotides and protein needed for
proliferation. Importantly, preliminary data has 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 test the hypotheses that
aspartate is an endogenous metabolic limitation for some tumors (Aim 1), that reductive glutamine metabolism
supports aspartate production in hypoxic cells (Aim 2), and that 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 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. This
career development award will also be critical to my development as a scientist by providing me with mentored
training period at the renowned Koch Institute for Integrative Cancer Research at Massachusetts Institute of
Technology. This time will be used to develop my scientific ideas and increase my competency in working with
the mouse models of cancer that most faithfully recapitulate human disease. The scientific advances learned
from this proposal and the training period will be critical to my ultimate goal of establishing an independent
research group studying the metabolic constraints of cancer cell proliferation.

## Key facts

- **NIH application ID:** 9838731
- **Project number:** 5R00CA218679-03
- **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:** $223,720
- **Award type:** 5
- **Project period:** 2018-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838731

## Citation

> US National Institutes of Health, RePORTER application 9838731, Metabolic Constraints on Cancer Cell Proliferation (5R00CA218679-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9838731. Licensed CC0.

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