# Research Project 1: Enhancing neoadjuvant therapy to prevent breast cancer recurrence

> **NIH NIH U54** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $375,574

## Abstract

RESEARCH PROJECT 1: Enhancing Neoadjuvant Therapy To Prevent Breast Cancer Recurrence
PROJECT SUMMARY
Based on our strong preliminary and published data, our overarching hypothesis guiding the project is that agents
that enhance response to neoadjuvant combination chemotherapy will decrease recurrence rates by reduction
or elimination of minimal residual disease. These targeted agents may also function in combination with one
another, which may allow elimination of cytotoxic systemic chemotherapy. We further hypothesize that response
data can be used to refine computational methods for drug response prediction.
Aside from study of frank resistance to chemotherapies, which is also possible using our combined PDX platform,
study of minimal residual disease, as well as both local and distant recurrence is also important, particularly in
PDX derived from racial groups whose disease outcomes are worse than those in Caucasian women (i.e. African
American and Hispanic women). Under our current PDTC, we have already identified seven PDX as recurrent
after apparent complete response (CR) to combination carboplatin/docetaxel. We will apply a refined set of
computationally determined predictive signatures of differential response to carboplatin and taxanes (paclitaxel
going forward to match an upcoming clinical trial) to the remainder of TNBC in our combined PDX collection,
as well as to TNBC PDX to be created in both PDTC projects to identify PDX most likely to show complete
response to the combination. Importantly, response to either carboplatin or docetaxel correlates with response to
their combination 86% of the time. Existing and new PDX will be evaluated for CR and recurrence in response
to combination chemotherapy in Aim 1, with the ultimate goal of identifying a total of at least 20, but optimally
30, recurrent PDX models for testing of the ability of targeted agents computationally predicted to augment
chemotherapy response in Aim 2 to reduce or prevent recurrence in Aim 3.

## Key facts

- **NIH application ID:** 10909331
- **Project number:** 5U54CA224076-06
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Michael T. Lewis
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,574
- **Award type:** 5
- **Project period:** 2017-09-25 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909331

## Citation

> US National Institutes of Health, RePORTER application 10909331, Research Project 1: Enhancing neoadjuvant therapy to prevent breast cancer recurrence (5U54CA224076-06). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10909331. Licensed CC0.

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