# Novel Tools for Colon Cancer Detection and Therapy

> **NIH VA I01** · OMAHA VA  MEDICAL CENTER · 2024 · —

## Abstract

Colorectal cancer (CRC) is the third major cancer in the USA and accounts for 9.5% of all the
cancers among the Veterans. Polypectomy during screening colonoscopy has significantly
reduced both the CRC incidence and associated patient mortality. However, despite the
significant progress, the CRC risk reduction remains suboptimal and specifically worse in relation
to CRC arising in the right colon. Although quality metrics in endoscopy have focused on
improving detection of standard adenomas, there is a lack of concordance between the
conventional adenoma detection rate and ability to visualize sessile serrated polyps underscoring
the need for adjuvant approaches. Also, despite high R0 resection rates in patients with CRC,
local and distant recurrence is still a significant problem and has been cited as high as 40%. The
complete resection of tumor is critical to patient outcomes. We and others have shown that
Claudin-1(CLDN-1), a tight junction (TJ) protein, expression increases in colorectal cancer (CRC)
in stage specific manner, and is highly upregulated during colon cancer progression and
metastasis. Several studies have further validated a causal role of Claudin-1 colon cancer
progression and metastasis in vitro and in vivo. In brief, CLDN1 expression increases in a stage
specific manner and an upregulated CLDN1 expression characterizes both, pre-malignant SSA/P
adenomas and CRC metastasis. Notably, in our study, 8 out of 9 metastatic patients derived
orthotopic xenografts (PDOX) demonstrated high CLDN1 expression. We further demonstrated
that using antibody-guided imaging anti-CLDN1 antibodies conjugated to NIR fluorophores clearly
labeled tumor and liver metastases enabling successful fluorescence-guided surgery (FGS).
Similar ability of CLDN1 fluorescent peptides for detection of CRC adenomas was reported by
another lab. Taken together, we hypothesize that intraoperative use of CLDN-1-targeted near-
Infrared fluorescent (NIRF) imaging probes will improve the detection of high-risk pre-malignant
adenomas and CRC metastasis, and also improve their resection. To this hypothesis, we propose
following specific studies: SPECIFIC AIM 1: To synthesize, characterize, and perform the pre-
clinical safety evaluation of CLDN-1 antibodies-conjugated to NIR fluorophores. The antibody-dye
conjugate ratio providing maximum tumor signal, minimum short and long-term tissue retention,
and lowest toxicity will be established for pre-clinical studies. SPECIFIC AIM 2: Assessment of
the pre-clinical and clinical efficacy of CLDN-1-targeted imaging probes in polyps and CRC
metastasis. The clinical-guiding efficacy of CLDN-1-NIRF probes will also be validated in surgical
samples from adenomas and metastatic tumor tissues using ex vivo imaging of patient tissues.
Characterization of the key molecules involved in the processes critical for CRC progression to
develop novel early detection and therapeutic approaches would not only decrease patient
mortality among VA-CR...

## Key facts

- **NIH application ID:** 10811569
- **Project number:** 5I01CX002228-02
- **Recipient organization:** OMAHA VA  MEDICAL CENTER
- **Principal Investigator:** Michael Bouvet
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811569

## Citation

> US National Institutes of Health, RePORTER application 10811569, Novel Tools for Colon Cancer Detection and Therapy (5I01CX002228-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10811569. Licensed CC0.

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