# Ex vivo slice cultures of mouse pancreatic tumors to test novel regimens

> **NIH VA I21** · JESSE BROWN VA MEDICAL CENTER · 2023 · —

## Abstract

While chemotherapy remains the standard treatment, there is an increasing interest in developing novel
regimens for pancreatic ductal adenocarcinoma (PDAC). Novel regimens, such as the combination of BET and
HDAC inhibitors targeting epigenetic changes, are often tested initially in mouse models. However, mouse
models have several limitations. With an ever-increasing number of drugs being developed for cancer, how best
to evaluate these drugs in mouse models, either alone or in combination regimens, can also be quite daunting.
Recently, ex vivo tissue slices of human tumors have been utilized for therapeutic studies, but one of the
significant challenges of slice cultures with human PDAC tumors is the limited availability of fresh human PDAC
tumors for research studies. As there is an urgent need to identify effective regimens for PDAC patients, slice
cultures from PDAC tumors developing in transgenic mouse models may overcome the limitations of both mouse
models and ex vivo slice cultures of human PDAC tumors. The main objective in this application is to validate
slice cultures from PDAC tumors developing in transgenic mouse models as a means of testing novel regimens
for pancreatic cancer. The central hypothesis is that slice cultures established from mouse PDAC tumors will
readily allow the testing of novel regimens for pancreatic cancer. The rationale for the proposed research is that
validating slice cultures from mouse PDAC tumors will accelerate the screening and identification of novel
regimens for PDAC patients. Two specific aims are proposed: 1) Validate ex vivo slice cultures established from
mouse PDAC tumors by testing approved chemotherapies. 2) Validate ex vivo slice cultures established from
mouse PDAC tumors by testing the combination of BET and HDAC inhibitors. Under the first aim, chemotherapy
regimens that have previously been shown to be effective in vivo in mouse models and human PDAC tumors
will be tested in ex vivo slice cultures of tumors established from three different transgenic mouse models of
PDAC. In addition, we will evaluate the effectiveness of adding targeted inhibitors to chemotherapy in ex vivo
slice cultures of PDAC tumors from transgenic mice. In the second aim, the combination of BET and HDAC
inhibitors will be tested in ex vivo slice cultures of tumors established from three different transgenic mouse
models of PDAC. In addition, we will evaluate the relative efficacy of combining BET inhibitors with chemotherapy
in the ex vivo tumor slice cultures. There are several innovative elements in this proposal, including the novel
concept of using ex vivo slice cultures of mouse tumors to test various combination therapies for PDAC. This
proposed research is significant because validating ex vivo slice cultures of mouse tumors to identify novel
regimens will have important clinical-translational implications for PDAC patients.

## Key facts

- **NIH application ID:** 10653683
- **Project number:** 5I21BX005693-02
- **Recipient organization:** JESSE BROWN VA MEDICAL CENTER
- **Principal Investigator:** Hidayatullah G. Munshi
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10653683

## Citation

> US National Institutes of Health, RePORTER application 10653683, Ex vivo slice cultures of mouse pancreatic tumors to test novel regimens (5I21BX005693-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10653683. Licensed CC0.

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