# Enhancing anti-EGFR Therapeutic Efficacy in Inflammatory Breast Cancer

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $366,000

## Abstract

Inflammatory breast cancer (IBC) is the most lethal and aggressive form of breast cancer, and metastasis is
the major cause of death in patients with IBC. To date, there are no FDA-approved targeted therapies that are
specific for patients with IBC, and the molecular mechanism underlying IBC’s aggressiveness is not well
understood. The long-term goal of the applicant’s group is to decrease the mortality associated with IBC by
developing a novel therapy. The overall objectives of this application are to determine how the EGFR pathway
promotes the progression of IBC and, through understanding the pathway, to identify novel therapeutic targets
that could enhance the efficacy of EGFR targeted therapy. The central hypothesis is that the EGFR pathway is
highly exploitable as a therapeutic target in IBC because this pathway promotes inflammation and cancer
stem-like cell (CSC) self-renewal. The rationale for the proposed research is that identifying and validating
novel targets will lead to the development of an efficacious combination-therapy approach to prolonging the
survival of patients with IBC. On the basis of strong preliminary data, the hypothesis will be tested by pursuing
two specific aims: 1) Determine how the EGFR/COX-2 signaling axis regulates the CSC population in IBC
cells; and 2) Determine predictive biomarkers of response to EGFR targeted therapy in patients with IBC. In
the first aim, the effect of EGFR/COX-2 activation or inhibition on the IBC CSC population through the
mediation of Nodal/TGFβ signaling and the involved mechanism will be investigated. Further, potential
combination approaches that could enhance the efficacy of EGFR targeted therapy will be identified. In the
second aim, the role of EGFR/COX-2/TGFβ axis molecules in predicting the response to PmAb will be
determined, and the impact of PmAb on regulating the cross-talk between tumor cells and the adjacent
microenvironment will be investigated. In addition, for patients receiving EGFR targeted therapy, RNA
sequencing of before- and after-treatment samples will be performed to compare the differential gene
expression profiles between patients who achieve pathological complete response and those who do not. The
proposed research is innovative because it focuses on the unique molecular features of IBC and uses a novel
approach of targeting CSC in IBC through EGFR and/or inflammatory-related pathways; also, it utilizes a novel
multiplexed immunostaining imaging technology that allows multiple sets of markers to be visualized within the
same cells or tissue section. The proposed research is significant because it is expected to fundamentally
advance the understanding of IBC and facilitate the development of a novel personalized therapy, leading to
much more effective clinical trials for IBC and ultimately, reduced mortality from IBC. The regimen established
from this work will also be adopted in a clinical trial for chemoresistant primary non-inflammatory breast
cancers with ...

## Key facts

- **NIH application ID:** 9852888
- **Project number:** 5R01CA205043-04
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Naoto T. Ueno
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $366,000
- **Award type:** 5
- **Project period:** 2017-03-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852888

## Citation

> US National Institutes of Health, RePORTER application 9852888, Enhancing anti-EGFR Therapeutic Efficacy in Inflammatory Breast Cancer (5R01CA205043-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852888. Licensed CC0.

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