# Microvasculature in Colon Field Carcinogenesis: Clinical-Biological Implications

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $613,159

## Abstract

Project Summary
The overall goal of this project is to develop a rectal probe for minimally intrusive highly accurate risk stratification
with the vision of utilizing it for a precision medicine approach to colon cancer screening and also potentially
chemoprevention (companion biomarker). We will employ cutting edge biophotonics (ISOCT) and biological
approaches combined with large scale human studies to elucidate the clinical/biological implications of mucosal
early increase in blood supply (EIBS). Our multi-disciplinary group has extensively reported on EIBS in two
animal models and human studies (n>1000) through the development of cutting-edge biophotonics technology
namely the polarization gated spectroscopy (PGS) and more recently inverse spectroscopic optical coherence
tomography (ISOCT). Clinically, rectal EIBS had excellent diagnostics of advanced adenomas (AUC >0.8) albeit
impacted somewhat by race and gender. Biologically, our data on early colonic mucosal metabolic
reprogramming (Warburg like effect) in both animal models and humans provides a potential mechanism for
EIBS. For Causational Insights, pilot animal studies demonstrated that targeting microcirculation with the
angiotensin receptor blocker losartan decreased EIBS with a concomitant suppression of colonic tumorigenesis.
Furthermore, chemopreventive agents appear to reverse the Warburg-like physiology in the premalignant colonic
mucosa. We hypothesize that EIBS is a manifestation of metabolic reprogramming that can be detectable with
unprecedented accuracy with ISOCT. In aim 1 (technology), we will develop and validate the ISOCT fiberoptic
probe and ascertain its accuracy for determining hemoglobin concentration, oxygenation status and blood vessel
diameter at various superficial tissue depths. In aim 2 (biomarker), we will develop and validate a rectal EIBS
prediction rule for the presence of advanced adenomas with prediction rule optimized for gender & race using
biomarkers related to hemoglobin oxygenation, depth and blood vessel radius and density aiming for sensitivity
& specificity ≥90%. For metabolic physiological correlates, we will interrogate the short term primary colon biopsy
cell cultures via the extracellular flux analysis (Seahorse) as a physiological marker of Warburg. We will correlate
with ISOCT readings and neoplasia presence (race/gender specific) along with the expressions of genes
implicated in Warburg. In aim 3 (causational insight), we will perform animal studies to determine whether
targeting the EIBS and secondary metabolic events using losartan (angiotensin 2 inhibitor) and metformin
(promising chemopreventive agent known to reverse Warburg effects) would be a potential adenoma prevention
strategy. Biologically, this study will provide definitive confirmation that EIBS is an important effector of metabolic
reprogramming in colon carcinogenesis. Clinically, a rectal EIBS would be minimally intrusive and could be
employed in the primary care setting to...

## Key facts

- **NIH application ID:** 10111477
- **Project number:** 5R01CA224911-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Vadim Backman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $613,159
- **Award type:** 5
- **Project period:** 2018-03-05 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111477

## Citation

> US National Institutes of Health, RePORTER application 10111477, Microvasculature in Colon Field Carcinogenesis: Clinical-Biological Implications (5R01CA224911-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10111477. Licensed CC0.

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