# Attacking stress tolerance in cancer

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $945,158

## Abstract

Project Summary/Abstract
My career began with the identification of cell surface markers on invasive cells, and led to the discovery of
how integrins αvβ3 and αvβ5 on endothelial cells respond to cues within the tumor microenvironment to
promote angiogenesis. I later demonstrated that αV integrins on tumor cells use these same fundamental
pathways to achieve aggressive, invasive, and metastatic behavior. Now, my R35 proposal represents a
further evolution of these concepts to ask how tumor cells undergo reprogramming in response to cellular
stresses, including hypoxia, nutrient deprivation, or cancer therapy. We find that αvβ3 expression can be
induced by stress to reprogram tumor cells toward a stress-tolerant, drug-resistant, stem-like state that is
associated with tumor progression and metastasis for a wide range of cancers. Because individual tumors use
this integrin to overcome unique challenges, we will define how αvβ3 activates downstream effectors that vary
between tumor type, genetic profile, and microenvironment. The overall goal of my future research program is
to understand how such tumors use integrin αvβ3 to gain stress tolerance so that we can devise ways to attack
this process therapeutically. This proposed research will not only lead to a fundamental understanding of how
tumors adapt to therapy or microenvironmental stress, but it should identify new druggable targets to limit
cancer progression by preventing or overcoming tumor cell drug resistance and stress tolerance.

## Key facts

- **NIH application ID:** 9996520
- **Project number:** 5R35CA220512-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** DAVID A CHERESH
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $945,158
- **Award type:** 5
- **Project period:** 2018-09-18 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996520

## Citation

> US National Institutes of Health, RePORTER application 9996520, Attacking stress tolerance in cancer (5R35CA220512-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9996520. Licensed CC0.

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