# Developing a Human in Mouse Cancer Model with a Completely Humanized Stroma

> **NIH NIH R01** · MAGEE-WOMEN'S RES INST AND FOUNDATION · 2020 · $79,960

## Abstract

Abstract
Mouse models of cancer are easy to use, reproducible, and have manageable costs. Mice can also be
genetically engineered to study specific oncogenic pathways. Given the many positives associated with murine
models, the vast majority of pre-clinical anti-cancer therapeutic studies are performed in a mouse.
Unfortunately, the vast majority of oncology drugs (~94%) that are effective in murine tumor studies will
ultimately fail when tested in humans. These failures cost billions of dollars and waste physician and patient
resources. Clearly, current preclinical mouse tumor models are not accurately predicting a patients’ response
to therapy. Thus current mouse models need to be improved to more accurately reflect human disease. Each
of the currently available mouse models of human cancer has distinct strengths, but also critical flaws. One
critical flaw in all available preclinical models is the lack of human tumor stroma. However, work from our
group and others demonstrates that human tumor stroma is a critical component of the human tumor
microenvironment which promotes human tumor growth, metastasis, suppresses anti-tumor immunity, and
induces therapeutic resistance.
Our long term goal is to develop a human tumor model that will, by better representing human tumors, will
better cancer therapeutic response seen in human clinical trials. We hypothesize that a human tumor model
with both human cancer cells and human tumor stroma will better represent primary human disease. As such,
it will be a better/more stringent model for preclinical drug screening that could ultimately prevent a drug which
is destined to fail from being used in clinical trials. We further hypothesize that human tumor stroma will better
maintain tumor cell heterogeneity over time to more accurately reflect the natural evolution of therapeutic
resistance. Finally such a model will be ideal for evaluating the impact of human tumor stroma on novel
immune cell therapies. We propose to use a combination of human adult stem cells and cancer associated
stem cells to create human tumor model with both human cancer cells and stromal cells. We will perform
extensive histological and molecular profiling to confirm this model reflects primary tumor. Finally, we will (i)
evaluate the models ability to predict patient response to disease in a retrospective study and (ii) assess the
use of this model to evaluate novel immunotherapies using a novel CAR T-cell construct targeting ovarian
cancer cells.

## Key facts

- **NIH application ID:** 10246576
- **Project number:** 3R01CA211913-03S1
- **Recipient organization:** MAGEE-WOMEN'S RES INST AND FOUNDATION
- **Principal Investigator:** Ronald J Buckanovich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $79,960
- **Award type:** 3
- **Project period:** 2017-09-05 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246576

## Citation

> US National Institutes of Health, RePORTER application 10246576, Developing a Human in Mouse Cancer Model with a Completely Humanized Stroma (3R01CA211913-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246576. Licensed CC0.

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