# Features of the early adenoma and adjacent colon that drive progression: the role of mutation burden in normal tissue, senescent cells, and tumor clonal architecture

> **NIH NIH U54** · FRED HUTCHINSON CANCER CENTER · 2024 · $455,640

## Abstract

PROJECT SUMMARY
CRC persists as a heavy burden in the United States and throughout the world with over 1.93 million new
cases and 0.95 million deaths in 2020. Our study is designed to identify autonomous and non-autonomous
attributes of the early adenoma and the surrounding colon that drive adenoma progression to malignancy. In
this project, we mimic in mice a primed colon with pre-existing mutant clones (Aim 1) or overloaded with
senescent cells (Aim 2) to determine whether these altered states enhance adenoma formation and
progression. Such attributes can be detected with modern technology, so individuals could be screened to
determine their personal risk of developing CRC. We propose that adenomas emerging from a primed colon
can have a multi-ancestral origin being derived from multiple progenitors. Interactions among intermingled
clones could alter gene expression in the participating clones in a manner that favors adenoma progression
(Aim 3). Such interactions could potentially be disrupted with new chemopreventive agents or repurposed
common drugs. Thus, individuals having a primed colon and consequently at a high risk of CRC could be
identified, surveilled more frequently, and potentially treated to prevent cancers from forming

## Key facts

- **NIH application ID:** 10926953
- **Project number:** 5U54CA274374-03
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Richard Brott Halberg
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $455,640
- **Award type:** 5
- **Project period:** 2022-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10926953

## Citation

> US National Institutes of Health, RePORTER application 10926953, Features of the early adenoma and adjacent colon that drive progression: the role of mutation burden in normal tissue, senescent cells, and tumor clonal architecture (5U54CA274374-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10926953. Licensed CC0.

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