# Optical imaging to predict cell-level genetic heterogeneity and treatment sensitivity in colorectal cancer

> **NIH NIH R37** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $582,807

## Abstract

PROJECT SUMMARY/ABSTRACT
Across all cancers a significant problem in oncology is the current lack of reliable means to predict response to
anti-cancer treatments for individual patients. Specifically in locally advanced rectal cancer (LARC), it is known
that patients can benefit from chemotherapy, radiation, and operative management. However, not all of these
therapies may be required for each individual patient. With standard practices, patients are exposed to the
toxicities of all of these modalities without knowing the necessity of each. In addition, for some patients they
require escalation of therapies beyond these due to resistant disease. A method to predict treatment response
is urgently needed to better tailor the neoadjuvant treatment paradigm for individual patients and this is the goal
of this proposal. The long-term objective of this proposal is to utilize optical metabolic imaging (OMI) of patient-
derived colorectal cancer (CRC) organoid cultures to predict sensitivity to therapeutic regimens. This proposal
develops novel cellular-level imaging technologies to predict treatment response in individual cancer patients
using optical metabolic imaging (OMI) of organoids cultures from their own tumors. Since tumor genetics can
have profound impacts on cellular metabolism, a better understanding of the underlying mechanisms by which
tumor genetics alter OMI in the pre- and post-treatment settings is needed. In addition, assessment of cell-level
heterogeneity within patient samples is required to fully predict the treatment response. To interrogate these
mechanistic inquiries, we have generated multiple tools and research techniques. Our data to date indicate that
OMI in primary CRCs and other tumor types predicts in vivo drug response in mice and patients.
In this proposal, we test the hypothesis that OMI of patient-derived organoid cultures will predict treatment
response for patients with CRC undergoing chemotherapy and/or radiation. In this extension proposal, we build
on the prior aims to assess the use of OMI to evaluate clonal evolution and correlate these studies with molecular
evolution of these cells. Additionally, we further validate the OMI response thresholds to predict treatment
response identified in our initial aims with an additional cohort of CRC patients. Finally, we will perform a
multivariate analysis to evaluate multiple OMI parameters in combination with change in organoid diameter,
response on clinical imaging, pre-treatment clinical stage, age, gender, race/ethnicity, clinical treatment dose
intensity, tumor infiltrating lymphocyte counts, and the molecular profile as predictors of clinical outcomes for
these CRC patients. Overall, these additional aims represent logical extensions of the initial aims and will be key
to further supporting the incorporation of OMI of patient-derived organoids into future prospective clinical trials.

## Key facts

- **NIH application ID:** 10880514
- **Project number:** 5R37CA226526-07
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Dustin A Deming
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $582,807
- **Award type:** 5
- **Project period:** 2018-06-08 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880514

## Citation

> US National Institutes of Health, RePORTER application 10880514, Optical imaging to predict cell-level genetic heterogeneity and treatment sensitivity in colorectal cancer (5R37CA226526-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10880514. Licensed CC0.

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