# Targeted therapeutics for ovarian cancer and its microenvironment - treatment and theoretical modeling

> **NIH NIH U01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $500,198

## Abstract

Project Summary
With the traditional therapies for ovarian cancer (OC) that include surgery followed by cytotoxic chemotherapy
patient survival is still extremely poor and 5-year survival rate is less than 30%. Therefore, new treatment
strategies are needed to cure or improve dismal patient survival. Recent clinical and experimental evidence
including ours indicate that the monocyte-macrophage axis (MMA) and tumor-associated macrophages
(TAMs) play a significant role in tumor growth and progression by contributing to angiogenesis,
invasion/metastasis, and drug resistance. We found OC patients with increased numbers of circulating
monocytes and intratumoral TAMs have poor clinical outcomes and significantly shorter patient survival. Our
studies also indicate that the tumor microenvironment and TAMs are attractive therapeutic targets in ovarian
and other cancers and reduction of TAMs inhibits angiogenesis, invasion and metastasis, and drug resistance
in ovarian cancer models. Overall data indicate that in contrast to the conventional drugs that target only tumor
cells, targeting tumor microenvironment is required to achieve maximal anti-tumor efficacy. Also, lack of critical
molecular targets for this purpose and together with a lack of effective delivery systems, biological barriers for
drugs, including poor tissue-specific delivery, toxicity, and the inability to deliver high concentrations of
therapeutics into tumor microenvironment, therapeutic strategies fail to cure OC. The use of siRNA bearing-
nanoparticles targeted to the tumor and the microenvironment is a particularly attractive approach for targeting
molecular targets, reprogramming the tumor microenvironment and development of the most effective
therapeutic strategies for OC. To directly address these unmet needs we recently developed various
nanoparticle (NP) platforms including, (1) long-acting, slow-release dual assembly NPs (DANPs); (2) serum
resistant AXL-receptor binding-aptamers for development of targeted therapies in OC and validated each NP-
based approach in multiple OC tumor models with robust and sustained target silencing and significant
antitumor efficacy. In this study we will test the hypothesis that the blockade of the tumor and tumor
microenvironment interactions by highly versatile NPs that encase therapeutic cargos will provide significant
antitumor activity and enhance the efficacy of current regimens in OC. Thus we will determine mechanism of
TAM regulation and determine the biological and therapeutic efficacy of targeting MMA/TAMs using highly
targeted dual effect NPs in OC models as well as by applying mathematical models.

## Key facts

- **NIH application ID:** 9937672
- **Project number:** 5U01CA213759-04
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Gabriel Lopez-Berestein
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $500,198
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937672

## Citation

> US National Institutes of Health, RePORTER application 9937672, Targeted therapeutics for ovarian cancer and its microenvironment - treatment and theoretical modeling (5U01CA213759-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9937672. Licensed CC0.

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