# Washington University PDX Development and Trial Center

> **NIH NIH U54** · WASHINGTON UNIVERSITY · 2021 · $119,999

## Abstract

Project Summary
 This application is being submitted in response to the Funding Opportunity Announcement (FOA) PA-
20-272. This supplemental proposal seeks to uncover the mechanism of synergy and develop an optimized
regimen of the combination of a microtubule-disrupting agent, eribulin, and a PI3K-inhibitor in patient-derived
xenograft (PDX) models of breast cancer. The work will be conducted as a national collaboration between
Washington University in St. Louis and BIDMC/Harvard Medical School in Boston. In her pre-clinical work, Dr.
Ma at Washington University in St. Louis has shown that the combination of eribulin and the PI3K-inhibitor
copanlisib greatly extends progression-free survival in eight PDX models of triple negative breast cancer
(TNBC). This novel concept is now being carried forward into a clinical trial in patients with metastatic TNBC
(NCT04345913). Her discovery was surprising as PI3K-inhibitor benefit so far had been restricted to
ER+PIK3CAmt breast cancer. The exact mechanism and, based on the mechanism, best timing of eribulin and
PI3K-inhibitor will be determined in the proposed work. This supplemental award will extend the work in
Research Project 1 in testing PI3K inhibitor combinations in breast cancer PDX models and to uncover
mechanisms of synergy for the combination of microtubule disrupting agent, eribulin, and the PI3K inhibitor,
copanlisib.
 Dr. Wulf's Parent R01 Proposal entitled “Novel Uses for PI3K-inhibitors for the Treatment of Advanced
PIK3CA-mutant Breast Cancer (1R01CA226776)” is slated to develop PI3K-inhibitor (PI3Ki) combinations for
patients with PIK3CAmutant breast cancer. PIK3CA-mutant breast cancer can be targeted with alpelisib, a
recent FDA-approved PI3K-an inhibitor now widely used in the metastatic setting in conjunction with estrogen
receptor blockade. In this project, we hypothesize that PI3K-inhibition is a metabolic intervention that, if applied
strategically following microtubule disruption, can deepen and prolong remissions obtained with microtubule
disrupting drugs, which are widely used to treat metastatic breast cancer. We will employ in vitro imaging and
metabolomic studies and in vivo imaging with 18FDG-glucose and 13C-pyruvate to deep-probe glycolysis in
response to chemotherapy, PI3K-inhibition and their combination and test if these imaging modalities can
predict responses. The team at WashU (Dr. Cynthia Ma, medical oncology and preclinical mouse work, Dr.
Kooresh Shogi (quantitative PET-imaging), Dr. Cornelius von Morze (quantitative MRI imaging) and at
BIDMC/Boston (Dr. Gerburg Wulf, pre-clinical mechanistic studies and Dr. Aaron Grant, pioneer in 13C-
pyruvate imaging) have established a MTA for transfer of the PDX models and will conference bi-monthly to
make this supplemental project happen within a year.

## Key facts

- **NIH application ID:** 10371645
- **Project number:** 3U54CA224083-03S2
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Li Ding
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $119,999
- **Award type:** 3
- **Project period:** 2021-05-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371645

## Citation

> US National Institutes of Health, RePORTER application 10371645, Washington University PDX Development and Trial Center (3U54CA224083-03S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10371645. Licensed CC0.

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