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

> **NIH NIH R33** · UNIVERSITY OF AKRON · 2021 · $59,188

## 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 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 matrix invasion of cancer cells. These studies will use engineered tumor models of
both TNBC cell lines and patient-derived CAFs to establish the feasibility of tailoring our tumor model to
patient-specific cells. Through this research, we expect to establish our tumor model as a transformative
advance that will be implemented broadly for drug discovery and mechanistic studies of breast cancer.

## Key facts

- **NIH application ID:** 10337608
- **Project number:** 3R33CA225549-03S1
- **Recipient organization:** UNIVERSITY OF AKRON
- **Principal Investigator:** Gary D Luker
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $59,188
- **Award type:** 3
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337608

## Citation

> US National Institutes of Health, RePORTER application 10337608, A High Throughput Human Tumor Modeling Technology for Cancer Drug Discovery (3R33CA225549-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10337608. Licensed CC0.

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