# Project 3: The Role of Macrophages in Resistance to Anti-VEGF Drugs in Ovarian Cancer

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $344,532

## Abstract

Project 3 SUMMARY/ABSTRACT 
Angiogenesis is known to play a critical role in cancer growth and metastasis. Among the many potential 
targets, vascular endothelial growth factor (VEGF) has been well recognized to play an important role in 
angiogenesis, and drugs targeting this pathway have been used against ovarian and other cancers. Clinical 
use of anti-VEGF therapy, however, has yielded only modest improvement in progression-free or overall 
survival of patients with ovarian cancer, likely due to adaptive changes in the tumor microenvironment. There 
remains an unmet need to develop methods to enhance efficacy of anti-VEGF therapy and block growth- 
promoting adaptive changes. The mechanisms of adaptive resistance to anti-VEGF treatment are largely 
unknown. Understanding the adaptive resistance to anti-VEGF treatment has the potential to significantly 
enhance the efficacy of anti-VEGF therapy in ovarian cancer patients. Our preliminary findings suggest that 
tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are substantially 
increased in the anti-VEGF therapy-resistant tumors and TAM depletion (with CSF1R inhibitor) can improve 
the effectiveness of anti-VEGF therapy; however, the mechanisms by which this occurs are not well 
understood. In this proposal, we will explore the mechanisms by which macrophages contribute to adaptive 
resistance to anti-VEGF treatment and test the efficacy of dual targeting of VEGF and TAMs/MDSCs. Our 
central hypothesis is that targeting TAMs in the microenvironment will reverse the immunophenotypical 
alterations induced by bevacizumab and improve clinical efficacy. We will conduct a novel, induction, 
randomized supplementation clinical study to assess the impact of adding a CSF1R inhibitor to identify and 
overcome these effects as measured by objective response and event-free survival. The proposed work is 
highly translational and has the potential to significantly enhance the efficacy of anti-VEGF therapy in ovarian 
cancer patients.

## Key facts

- **NIH application ID:** 10251116
- **Project number:** 5P50CA217685-05
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** ANIL K SOOD
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $344,532
- **Award type:** 5
- **Project period:** 2017-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251116

## Citation

> US National Institutes of Health, RePORTER application 10251116, Project 3: The Role of Macrophages in Resistance to Anti-VEGF Drugs in Ovarian Cancer (5P50CA217685-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10251116. Licensed CC0.

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