# Novel mechanisms and predictors of VEGF receptor inhibitor-associated hypertension

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $646,539

## Abstract

Project Summary (Limit 30 lines)
Tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor (VEGFR) signaling
pathway have emerged as important therapeutics in oncology with a total of nine such VEGFR-TKI having
been approved in the last decade. Despite considerable efficacy, VEGFR TKIs are associated with
hypertension and other cardiovascular sequalae. Currently, little consensus exists for predictors as well as for
preventive and treatment strategies for VEGF-TKI associated hypertension. This proposal is in response to the
NIH Funding opportunity announcements (FOA) that encourages collaborative applications that contribute to
the identification and characterization of patients at risk of developing cancer treatment-related cardiovascular
toxicity. Using the Vanderbilt cardio-oncology program as a platform, we have assembled a team with the goal
of understanding the mechanisms of VEGF-TKI associated hypertension and to develop precision preventive
and treatment strategies. We hypothesize that interactions between VEGFR and endothelin-1 (ET-1) signaling
impact hypertension and vascular dysfunction in VEGF-TKI associated hypertension. In basic studies, we
investigate the mechanism by which VEGF signaling regulates ET-1 transcription and expression (aim 1). In
correlative clinical and translational studies, we will determine the impact of endothelin receptor antagonism on
VEGF-TKI hypertension using approved drugs (aim 2). Our unique approach addressing the toxicities
associated with this class of cancer therapies could have implications for studying cardiac issues that arise
from other cancer therapies, especially as these are being combined for use with VEGFR-TKI.

## Key facts

- **NIH application ID:** 10554695
- **Project number:** 7R01HL141466-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Javid J Moslehi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $646,539
- **Award type:** 7
- **Project period:** 2022-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10554695

## Citation

> US National Institutes of Health, RePORTER application 10554695, Novel mechanisms and predictors of VEGF receptor inhibitor-associated hypertension (7R01HL141466-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10554695. Licensed CC0.

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