# Rapid and flexible precision oncology mouse models of epithelial malignancies epithelial malignancies

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2021 · $488,090

## Abstract

Genome characterization has enabled the cataloging of genes altered in human tumors and stimulated the
development of therapies that exploit these alterations. Still, functional studies are ultimately needed to interpret
and exploit the genetic variation that exists in human cancers. Furthermore, it is now apparent that cancer
phenotypes and responses to therapy are dramatically influenced by the tissue microenvironment, and hence it
is necessary to have in vivo models that accurately recapitulate both the genetics and physiology of cancers in
patients. Although existing genetically engineered mouse models (GEMMs) have been instrumental in validating
cancer-promoting mutations and developing therapeutic concepts in a physiological and relevant context, these
models are simply too slow and expensive to be broadly useful and only recapitulate a minor fraction of the
genetic lesions associated with human cancer. Driven by the need for more accurate and facile models, this
project combines CRISPR genome engineering and in vivo organ electroporation with the goal of producing the
first-in-kind collection of genetically-defined mouse models of three major epithelial malignancies. We refer to
these models as electroporation-based genetically engineered mouse models (EPO-GEMMs). EPO-GEMMs
have a range of advantages over traditional GEMMs in that they are fast, affordable, modular, highly portable,
and avoid the substantial waste associated with GEMMs produced by strain intercrossing. These models are
fully somatic, enable focal tumor development and, importantly, enable the study of tumor-host interactions by
allowing tumors to be rapidly engineered in hosts of different genetic backgrounds. Based on substantial
preliminary data to validate the EPO-GEMM concepts, our project will produce and characterize EPO-GEMMs
of stomach, prostate, and pancreatic cancer - three common human cancers for which existing mouse models
do not exist or are tedious. We will then perform a series of demonstration projects to evaluate and illustrate the
unique potential of the EPO-GEMM approach, ranging from testing the efficacy and toxicity of target inhibition,
exploring the effects of specific immune cell types on cancer initiation and progression, and using synchronous
cohorts of genetically defined cancer models to test new targeted therapies and immune oncology approaches.
Therefore, our project is of direct relevance to the overarching goals of the Oncology Models Forum, as EPO-
GEMMs constitute “translational research models that are robust representations of human biology, are
appropriate to test questions of clinical importance, and provide reliable information for patients’ benefit”. Each
of these models will be credentialed with the Oncology Model Fidelity Score and all reagents will be made
available through the NCIP Hub. We believe that the development and detailed characterization of rapid, flexible,
and immunocompetent EPO-GEMMs and the adoption of these models...

## Key facts

- **NIH application ID:** 10071141
- **Project number:** 5R01CA233944-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** SCOTT W. LOWE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $488,090
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071141

## Citation

> US National Institutes of Health, RePORTER application 10071141, Rapid and flexible precision oncology mouse models of epithelial malignancies epithelial malignancies (5R01CA233944-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071141. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*