# Optical imaging of pancreas cancer organoids for drug development and personalized treatment

> **NIH NIH R01** · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · 2020 · $790,207

## Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and poorly understood disease that has the
worst prognosis of all cancers (5 year survival of 7%), with more than 40,000 deaths per year in the US. Standard-
of-care treatment for PDAC includes surgery and chemotherapy. Many patients receive chemotherapy after
surgery (“adjuvant treatment”), to improve progression-free survival. About 45-55% of patients present with
metastatic disease and immediately begin chemotherapy if tolerated. Unfortunately, there are significant
toxicities associated with chemotherapy, and there are no tools to determine whether a patient will benefit from
a more toxic versus a less toxic drug. Additionally, there is no rational system to match each patient with the
most promising new drug for their cancer. Finally, there are few effective drugs for PDAC, and therefore a
demand for accelerated drug development. Thus, there is a critical need to improve the care of PDAC patients
through reduced toxicities, rational treatment planning, and new drug development.
 The goal of this proposal is to develop novel cellular-level imaging technologies to predict treatment response
in individual PDAC patients, using macro-suspensions of the patients’ tumors maintained in a 3D culture
(“organoids”). This non-invasive optical metabolic imaging (OMI) approach exploits the intrinsic fluorescence
intensity and lifetime of the metabolic co-enzymes NADH and FAD to image drug response on a single-cell level
across all cells in the intact 3D sample. This single-cell analysis allows for heterogeneous drug response to be
monitored over a treatment time-course in tumor cells and stromal cells. This is important for assessing treatment
efficacy in the highly heterogeneous and stromal micro-environment of PDAC. The use of primary tumor
organoids derived from the patients’ own tumor also maintains the cell-cell communication, 3D architecture, and
tumor-stromal interactions that are critical to accurately assess drug response. Our preliminary data indicate that
OMI in primary PDAC organoids (1) accurately predicts in vivo drug response in mice, and (2) can identify drugs
that effectively target tumor fibroblasts for stromal re-organization and improved drug delivery. We have also
established feasibility for human testing in 6 PDAC patients. This novel platform provides great potential for (1)
rapidly testing new drug regimens on relevant patient samples, thus accelerating PDAC drug development, and
(2) providing individualized drug screens to identify the most effective and least toxic treatment for each patient.
This proposal will test the hypothesis that OMI of primary PDAC organoids can accurately predict in vivo
treatment efficacy in mice and humans. This approach will be validated on mouse models of PDAC, on primary
patient samples in the adjuvant treatment setting, and on primary patient samples in the metastatic treatment
setting. The proposed development of dynamic, single-cell assessme...

## Key facts

- **NIH application ID:** 9961546
- **Project number:** 5R01CA211082-04
- **Recipient organization:** MORGRIDGE INSTITUTE FOR RESEARCH, INC.
- **Principal Investigator:** Melissa Caroline Skala
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $790,207
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961546

## Citation

> US National Institutes of Health, RePORTER application 9961546, Optical imaging of pancreas cancer organoids for drug development and personalized treatment (5R01CA211082-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9961546. Licensed CC0.

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