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

> **NIH NIH R37** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $611,495

## 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. Beyond that for patients with metastatic colorectal cancer
(CRC) multiple standard and experimental therapies exist and a way to predict which patients will respond to
which therapies would be a major advance. Sensitivity testing would prevent patients from unnecessarytoxicities
and allow escalation of or alternative therapies for those with resistant disease. A method to predict treatment
response is urgently needed and this is the goal of this proposal. The long-termobjective of this proposal is to
utilize optical metabolic imaging (OMI) of patient-derived CRC spheroid 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 spheroid 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 including transgenic
murine CRC models possessing combinations of mutations in commonly altered genes, murine CRC spheroid
cultures, isogenic human CRC cells, and patient-derived spheroid cultures and xenografts. Our preliminary data
indicate that OMI in primary CRCs and other tumor types predicts in vivo drug response in mice. We have also
tested this platform in pilot studies using patient-derived CRC spheroids.
In this proposal, we test the hypothesis that OMI of patient-derived spheroid cultures will predict treatment
response for patients undergoing chemotherapy and/or radiation for CRC. Specifically, we determine how
individual genetic alterations within spheroids impact OMI pre- and post-treatment with chemotherapy and/or
radiation. Secondly, we evaluate the heterogeneity within CRC spheroid cultures with complex molecular profiles
using OMI pre- and post-treatment with chemotherapy and/or radiation. In addition, we test whether spheroid
response using OMI predicts clinical responsein patients undergoing neoadjuvant treatment for locally advanced
rectal cancer and for systemic therapies for patients with metastatic CRC. Patients will be enrolled in a registry
protocol prior to the initiation of therapy. The OMI predictions will be validated with the clinical outcomes based
on pathology and imaging cr...

## Key facts

- **NIH application ID:** 9928294
- **Project number:** 5R37CA226526-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Dustin A Deming
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $611,495
- **Award type:** 5
- **Project period:** 2018-06-08 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928294

## Citation

> US National Institutes of Health, RePORTER application 9928294, Optical imaging to predict cell-level genetic heterogeneity and treatment sensitivity in colorectal cancer (5R37CA226526-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9928294. Licensed CC0.

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