# CCSG Supplement: Early-Stage Surgeon Scientist (ESSP)

> **NIH NIH P30** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $204,375

## Abstract

This application is being submitted in response to the Notice of Special Interest (NOSI) identified
as NOT-CA-21-100.
Abstract
Patients with locally advanced rectal cancers face a difficult treatment course involving
neoadjuvant 5-FU based doublet or triplet chemotherapy, chemoradiotherapy therapy, and
eventual surgical resection. While rates of neoadjuvant chemotherapy induce a complete
regression of tumors in a significant subset of patients (30-40%), and is associated with
significantly improved long term survival, responses remain heterogeneous with both local and
distant failures. Recently, we and others have demonstrated specific bacterial taxa within rectal
cancers are associated with a diminished response to neoadjuvant therapy. These bacteria
have been shown to lead to the inactivation of common chemotherapeutics and have the ability
to form an immune exclusionary environment within rectal cancers. While these microbial
communities can be modulated in preclinical models leading to improved response and tumor
control; there is a significant gap in our understanding of the ability to modulate these microbes
in a clinical setting. Intriguingly, clearance of a common deleterious bacterium Fusobacterium
nucleatum (Fn) through 5-FU based chemotherapy has been shown to improve recurrence free
survival in a cohort of rectal cancer patients. To understand the influence of these microbes in
rectal cancer, we propose to study banked and prospectively collected tissue from a feasibility
study of the ability of metronidazole to selectively clear deleterious anaerobes, such as Fn, and
the effect this has to augment 5-FU Fn killing. This will be coupled with translational studies of
both the tumor immune microenvironment comparing the tumors of patients able to achieve
durable complete responses as compared to those with persistent viable tumor post
neoadjuvant therapy. Finally, we will study the spatial immune and bacterial profile of the tumors
of patients that either do or do not clear tumoral Fn to better understand barriers to clearing
these deleterious anaerobes and potentially improve outcomes and increase inclusion of watch
and wait protocols in the near future. We hypothesize this study will identify active immune
infiltrates correlate with response to neoadjuvant chemotherapy while inactive or absent
immune infiltrates will correlate with the presence of high-risk microbes and a lack of response

## Key facts

- **NIH application ID:** 10997066
- **Project number:** 3P30CA016672-48S3
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Giulio Francesco Draetta
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $204,375
- **Award type:** 3
- **Project period:** 1996-08-28 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997066

## Citation

> US National Institutes of Health, RePORTER application 10997066, CCSG Supplement: Early-Stage Surgeon Scientist (ESSP) (3P30CA016672-48S3). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10997066. Licensed CC0.

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