# Project 1: Interrogating Distinct Tumor-Initiating Cells in CRC

> **NIH NIH P50** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $404,764

## Abstract

PROJECT SUMMARY/ABSTRACT: P1. Interrogating Distinct Tumor-Initiating Cells
A major therapeutic barrier in advanced colorectal cancer (CRC) is tumor recurrence after treatment. The
“cancer stem cell hypothesis” posits that rare populations of cancer cells with stem cell characteristics, also
known as tumor-initiating cells (TICs), fuel tumor growth, resist therapy, and repopulate the tumor at distal
sites. In the normal colon, multiple stem cell populations exist in a reserve-to-active continuum. We
hypothesize that distinct TIC populations exist in CRC, and these distinct populations of TICs have different
clonogenic properties and tumor-repopulating potential. Using TICs marked by Lrig1 and Lgr5 to represent
reserve and active TICs, respectively, we will use novel single-cell approaches to investigate the behaviors of
these populations in the context of therapeutic intervention. First, we will determine whether there is a defined
directional hierarchy where reserve TICs give rise to active TICs versus mutual interconversion. Second, we
will determine whether TICs with malignant characteristics pre-exist in the primary tumor or if TICs acquire
these characteristics de novo as a result of treatment. Third, we will determine whether a signature derived
from TIC behaviors provides prognostic and/or predictive information for individuals with CRC. Our
translational goal is to apply a systems approach to predict likelihood of tumor recurrence based on properties
of TIC populations with the long-term goal of using combinatorial pathway alterations to target TIC behaviors.

## Key facts

- **NIH application ID:** 9975133
- **Project number:** 5P50CA236733-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Robert J. Coffey
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $404,764
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975133

## Citation

> US National Institutes of Health, RePORTER application 9975133, Project 1: Interrogating Distinct Tumor-Initiating Cells in CRC (5P50CA236733-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9975133. Licensed CC0.

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