# Nutrient Regulation of Cancer Cell Growth

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $663,928

## Abstract

SUMMARY
Renal cell cancer (RCC) is the most common type of kidney cancer, and despite therapeutic advances, mortality
remains high. While there are over a dozen RCC subtypes with different genomic drivers, metabolic
reprogramming is a shared feature of tumorigenesis and progression across most of the major forms of kidney
cancer and represents a targetable vulnerability in RCC. Our preliminary results show that RCCs and other
cancers rely on the amino acid asparagine for tumor mTORC1 activity and growth, and methods to deplete tumor
asparagine levels impair cancer cell proliferation and block cancer growth. Cancers acquire asparagine through
two main routes: 1) consumption from the environment, and 2) biosynthesis from aspartate via asparagine
synthetase (ASNS). Over the last 5 years, we found that simultaneous reduction of tumor asparagine
consumption and biosynthesis blocks growth of lung, breast, and pancreas cancers in mice. Tumor asparagine
consumption can be targeted using L-Asparaginase (ASNase), which hydrolyzes serum asparagine, or dietary
asparagine restriction, which reduces serum asparagine levels. Tumor asparagine biosynthesis can be targeted
using metformin, which through inhibiting complex I of the electron transport chain (ETC), reduces cancer cell
production of aspartate, an obligate substrate for ASNS biosynthesis of asparagine. In this renewal proposal,
we will investigate kidney cancer asparagine dependency to determine whether asparagine depletion can be
broadly applied to treat patients with various subtypes of RCC. We will also determine the mechanism by which
asparagine is sensed in cancer cells to impact mTORC1 activity and whether asparagine depletion impacts
immune cell activation within the RCC tumor microenvironment.

## Key facts

- **NIH application ID:** 10607912
- **Project number:** 2R01CA215185-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Heather Christofk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $663,928
- **Award type:** 2
- **Project period:** 2017-12-06 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10607912

## Citation

> US National Institutes of Health, RePORTER application 10607912, Nutrient Regulation of Cancer Cell Growth (2R01CA215185-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10607912. Licensed CC0.

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