# Center for Modeling Tumor Cell Migration Mechanics

> **NIH NIH U54** · UNIVERSITY OF MINNESOTA · 2020 · $1,768,788

## Abstract

Abstract
At their most fundamental level, cancers are initiated by genetic alterations that drive hyperactive cell division
and cell migration. A common therapeutic strategy has been to target the proteins in the often-mutated
signaling pathways that regulate cell proliferation. However, so far this strategy has achieved only limited
success despite large public and private investment, which is likely due to functional redundancies in signaling
pathways that give multiple avenues for the emergence of drug-resistance. An alternative strategy, which
defines the organizing framework of our Center, is to directly target the internal or external mechanical
machinery or structural elements that drive cell migration. As it is these elements that serve as the most
downstream convergence point of the upstream genetic alterations, disruption of these critical elements
provides viable, clinically-relevant targets. Since cell migration is a common feature of high-grade cancer, and
invasion and metastasis are the primary cause of cancer related death, our Center will focus on understanding
the fundamental mechanics and chemistry of how cells generate forces to move through complex and
mechanically challenging tumor microenvironments. By focusing directly on the “nuts and bolts” of cell
migration, we will be targeting the most vital and non-redundant part of the system. Specifically, we propose
integrated modeling and experiments to investigate the molecular mechanics of cell migration and how the
tumor microenvironment regulates disease progression as a function of the underlying carcinoma genetics. We
will experimentally test our computational cell migration simulator, v1.0 (CMS1.0) for the mechanical dynamics
of cell migration that will ultimately be used to: 1) identify novel drug targets/target combinations in silico, 2)
define molecular mechanical subtypes of tumors for patient stratification, 3) guide the engineering of in vitro
microsystems and in vivo animal models to better mimic the human disease, and 4) simulate tumor
progression under different potential treatment strategies. Finally, we will develop a simulator-driven reverse
genetics approach to elucidate the functional mechanical consequences of driver mutations and seek to
manipulate the physical characteristics of a tumor to simultaneously bias against immune suppressor cells and
promote the antitumor immune response.

## Key facts

- **NIH application ID:** 9987316
- **Project number:** 5U54CA210190-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** DAVID ANDREW LARGAESPADA
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,768,788
- **Award type:** 5
- **Project period:** 2016-08-17 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987316

## Citation

> US National Institutes of Health, RePORTER application 9987316, Center for Modeling Tumor Cell Migration Mechanics (5U54CA210190-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9987316. Licensed CC0.

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