# A High Throughput Human Tumor Modeling Technology for Cancer Drug Discovery

> **NIH NIH R33** · UNIVERSITY OF AKRON · 2020 · $370,110

## Abstract

Project Summary
Tumor stroma, encompassing both extracellular matrix (ECM) and cells, regulates essentially all aspects of
tumor growth and metastasis. Signaling among cancer cells, stromal cells, and ECM in tumors promotes
proliferation of cancer cells and drug resistance among other key outcomes. Therefore, disrupting stroma-
cancer cells signaling is essential to restoring drug sensitivity of cancer cells and improving outcomes for
patients. Despite this recognition, the lack of physiologic, high throughput human tumors models significantly
impedes drug development and discovery efforts targeting tumor-stromal interactions.
We will address this need by developing a high throughput tumor microtissue technology to recreate the
complexity of native tumors and enable drug testing against tumor-stromal signaling. This facile technology
is based on two-step robotic micropatterning of user-defined cancer cells, stromal cells, and ECM using a
polymeric aqueous two-phase system in 1536 microwell plates. A 3D mass of cancer cells is formed in an
aqueous nanodrop settled at the bottom of a microwell and immiscible from the immersion aqueous phase.
A second aqueous drop containing the stromal components is then dispensed to merge with the nanodrop
and surround the cancer cell mass to spontaneously generate a microtissue upon incubation. This approach
uniquely offers the flexibility of incorporating tissue-specific matrix proteins and different stromal cells to
reproduce physicochemical properties of tumors in vivo. We will validate this technology using triple negative
breast cancer (TNBC) as a disease model, demonstrating effects of carcinoma-associated fibroblasts (CAFs)
and ECM on proliferation and drug responses of cancer cells. With this technology, we will test effects of
disrupting tumor-stromal signaling on treatment efficacy against TNBC cells. These studies will use
engineered tumor models of both TNBC cell lines and conditionally reprogrammed cells generated from
cancer cells of patients with metastatic TNBC to establish the feasibility of using our TMT model system for
precision oncology. We will perform combinatorial drug screening using standard chemotherapeutics and
molecular inhibitors against signaling pathways active in cells of specific TNBC patients to inhibit stroma-
mediated proliferation and drug resistance of cancer cells, and validate the most effective treatments in mouse
xenograft models of human TNBC. Through this research, we expect to establish our TMT technology as a
transformative advance that will be implemented broadly for drug discovery, mechanistic studies of breast
cancer and other malignancies, and precision medicine.

## Key facts

- **NIH application ID:** 9878078
- **Project number:** 5R33CA225549-02
- **Recipient organization:** UNIVERSITY OF AKRON
- **Principal Investigator:** Gary D Luker
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,110
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878078

## Citation

> US National Institutes of Health, RePORTER application 9878078, A High Throughput Human Tumor Modeling Technology for Cancer Drug Discovery (5R33CA225549-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878078. Licensed CC0.

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