# Multiscale systems biology modeling to exploit tumor-stromal metabolic crosstalk in colorectal cancer

> **NIH NIH U01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $272,093

## Abstract

Project Summary: Colorectal cancer (CRC) remains one of the deadliest cancers in the United States, with a
5-year survival rate of 10% for patients with metastatic disease. Over 120,000 people are diagnosed with CRC
each year, leading to approximately 50,000 deaths. Even with the current standard of care, CRC patients have
a high rate of relapse, and resistance to therapy is a key contributor to their high morbidity and mortality.
 Interactions between tumor and stromal cells are a source of acquired drug resistance. Cancer-associated
fibroblasts (CAFs) are a dominant cellular component of the tumor stroma and play a significant role in drug
resistance by contributing to the altered metabolism that is a hallmark of CRC. Recent studies suggest
reciprocal metabolic reprogramming among CRC cells and CAFs. However, questions still remain regarding
the metabolic dependencies of these two cell populations in the context of treatment response. Thus,
quantifying the collective cell dynamics (i.e. cooperation or competition) of tumor and CAF cells in their
metabolic ecosystem may provide insight needed to develop optimal cancer therapies.
 Despite many computational models of colorectal cancer growth and progression, there is currently no
quantitative spatiotemporal description of the interactions between colon cancer cells and stromal cells, or the
metabolic dependencies of these two cell populations. The proposed research addresses this limitation by
developing an experiment-based, multiscale computational model of tumor-stromal metabolic interactions in
colon cancer. We hypothesize that exploiting tumor-stromal metabolic dependencies will enhance the effects of
therapeutic strategies to inhibit tumor growth. We will test this hypothesis by using a systems biology approach
and pursuing three aims that combine computational and experimental studies: (1) Develop computational
models of intracellular metabolic pathways in CRC cells and CAFs that promote colon cancer proliferation; (2)
Develop a spatial multiscale model of colon cancer cell growth, integrating the pathway models of tumor-CAF
metabolic crosstalk; and (3) Identify and validate treatment strategies that exploit tumor and CAF metabolism.
 This work applies a systems biology approach comprised of novel mathematical frameworks across scales,
quantitative imaging techniques, and physiologically-relevant preclinical models. We have assembled a
dynamic team of Principal Investigators to successfully complete this project, integrating expertise in
computational systems biology (lead by Finley) and modeling multicellular interactions in biochemical signaling
environments (lead by Macklin), driven by cutting-edge high-throughput experimental data in realistic
conditions (lead by Mumenthaler). As a result, this work will generate the first multiscale model that explicitly
accounts for molecular interactions between tumor and stromal cells in the context of colorectal cancer. We will
apply the model to i...

## Key facts

- **NIH application ID:** 10479146
- **Project number:** 5U01CA232137-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Stacey Deleria Finley
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $272,093
- **Award type:** 5
- **Project period:** 2018-09-13 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10479146

## Citation

> US National Institutes of Health, RePORTER application 10479146, Multiscale systems biology modeling to exploit tumor-stromal metabolic crosstalk in colorectal cancer (5U01CA232137-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10479146. Licensed CC0.

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