# Linked regulation of tumor angiogenesis and chemo-resistance

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $356,850

## Abstract

Project Summary
Angiogenesis is one of the hallmarks of cancer and a much-pursued therapeutic target.
Most anti-angiogenic agents in clinical use target VEGF, VEGF receptors, or related
tyrosine kinases, and have shown significant promise in the neoadjuvant context.
However incomplete inhibition, evasive mechanisms, increased metastasis, and the
development of resistance have limited long-term success, underscoring the need for a
better understanding of the nuances of angiogenic regulation and the identification of
new targets for therapy.
Recent evidence points to a role for the DNA Damage Repair (DDR) pathway in
pathological angiogenesis under conditions of hypoxic stress, as is observed in growing
tumors. The DDR pathway is also a recognized promoter of resistance to DNA
damaging cancer treatment such as chemotherapy and radiation. Here we propose a
novel molecular target, the Eyes Absent protein tyrosine phosphatase (EYA-PTP) to
simultaneously target tumor angiogenesis and chemo-resistance. In preliminary studies
we have shown that the EYA-PTP activity promotes DDR and angiogenesis, and that
inhibition of the EYA-PTP or deletion in host endothelial cells signficantly attenuates
tumor growth and angiogenesis. In this project we plan to (1) study the interplay between
host endothelial EYA, tumor angiogenesis, and chemo-resistance, and (2) use existing
and newly developed EYA-PTP inhibitors as anti-angiogenic and chemosensitzation
agents in cell–line based and patient-derived orthoptoic xenografts.
The overall impact of this proposal is that it will define a new pathway involved in both
tumor angiogenesis, and resistance to DNA damaging first-line therapies. Using both
genetic and chemical biology approaches we will have demonstrated that the EYA-PTPs
are tractable cancer therapeutic targets.

## Key facts

- **NIH application ID:** 10248475
- **Project number:** 5R01CA207068-05
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** RASHMI S. HEGDE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $356,850
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248475

## Citation

> US National Institutes of Health, RePORTER application 10248475, Linked regulation of tumor angiogenesis and chemo-resistance (5R01CA207068-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10248475. Licensed CC0.

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