# VEGF/Neuropilin-2 Signaling and Radioresistance in Triple-Negative Breast Cancer

> **NIH NIH F30** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $33,758

## Abstract

PROJECT SUMMARY
Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer with standard therapy involving
neoadjuvant chemotherapy, surgical management, and radiation therapy. However, the high recurrence rate and
low pathological complete response of TNBC suggest that radioresistance is a critical factor in the diminished
therapeutic efficiency of the current treatment strategy. There is limited literature exploring the specific pathways
responsible for radiation resistance in TNBC, but most data support the role of limiting reactive oxygen species
(ROS) accumulation. Our lab has studied the role of Vascular Endothelia Growth Factor (VEGF) binding to
Neuropilin-2 (NRP2) and initiating several cancer stem cell properties. Preliminary data indicate that radiation
enriches for NRP2 expressing cells and using a function blocking antibody specific to VEGF/NRP2 with
irradiation decreases cell viability compared to either treatment alone in a TNBC organoid. The central
hypothesis of this proposal is that VEGF/NRP2 induces radioresistance by altering redox homeostasis and
can be targeted for better therapeutic outcomes in TNBC. This proposal will seek to investigate a possible
role of NRP2 regulating NOS2 transcription and its contribution to mitigating ROS accumulation. I will also use
single-cell RNA sequencing technology to identify the subpopulations of TNBC that are radioresistant and
whether they utilize the NRP2/NOS2 signaling axis. Another aspect of this proposal is to observe the
effectiveness of a function blocking antibody of NRP2 with radiation using an in vivo model. I plan to identify if
this approach reduces the radioresistant clones in TNBC. The completion of this proposal will heighten the
understanding of radioresistance in TNBC and identify a novel molecular pathway responsible for this phenotype.

## Key facts

- **NIH application ID:** 10887394
- **Project number:** 5F30CA275327-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Ayush Kumar
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $33,758
- **Award type:** 5
- **Project period:** 2023-06-28 → 2027-03-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887394

## Citation

> US National Institutes of Health, RePORTER application 10887394, VEGF/Neuropilin-2 Signaling and Radioresistance in Triple-Negative Breast Cancer (5F30CA275327-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10887394. Licensed CC0.

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