# Acquired Resistance to Therapy and Iron (ARTI) Center

> **NIH NIH U54** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $1,289,134

## Abstract

Overall Summary
Approximately 50% of cancer patients are treated with radiation therapy (RT), but local recurrence can still occur
even with the use of advanced RT techniques. This local recurrence, which commonly develops in 30-50% of
cancer cases, is exacerbated by the acquisition of RT resistance. This RT resistance is especially true for
patients with locally advanced thoracic cancers, such as lung and esophageal cancers. RT can lead to an iron-
dependent cell death modality, called ferroptosis, but whether ferroptosis resistance occurs within tumors giving
rise to acquired RT resistance is not known and is the central theme of the proposed Acquired Resistance to
Therapy and Iron (ARTI) Center. The overarching goals of the ARTI Center are: 1) to bridge the basic science
mechanisms of ferroptosis in acquired resistance with translational research in preclinical models and human
patient samples; 2) to identify cohorts of patients who are at greatest risk to develop acquired RT resistance;
and 3) to investigate the ability of novel therapeutic agents to re-sensitize lung and esophageal cancer cells to
radiation by inducing ferroptosis. The ARTI Center comprises two basic/mechanistic projects (Project 1 and
Project 2), one preclinical/translational project (Project 3), and one shared resource core (Molecular Imaging
Core [MIC]). Project 1 will focus on elucidating whether ferroptosis evasion is a key driver in acquired RT
resistance using radioresistant lung cancer and esophageal cancer cell lines and xenograft models that will be
used in Project 2. Project 2 will test the hypothesis that hypoxia, a long-recognized driver of tumor
radioresistance, suppresses ferroptosis induction during RT and contributes to RT-induced acquired resistance
to ferroptosis. Furthermore, expression of hypoxia-related genes and other targets of acquired RT resistance will
be analyzed by single-cell sequencing in Project 3. Project 3 investigates changes in immune cells in the tumor
microenvironment of humanized tumor models derived from chemoradiation therapy-responsive or -non-
responsive esophageal adenocarcinoma patients. These ferroptosis-mediated immunologic changes in the
tumor microenvironment may serve as prognostic biomarkers for identifying tumors that may acquire RT
resistance and predicting cancer patient outcomes, which could, in the future, be modulated by the ferroptosis-
inducing agents tested in Projects 1 and 2. Projects 1, 2, and 3 will be supported by the MIC that utilizes
bioluminescence imaging to monitor tumor growth, positron emission tomography (PET) tracers to monitor
cystine transporter activity and to identify hypoxic regions within tumors, as well as novel, redox-tuned PET
tracers for identifying activated innate immune cells. The ARTI Center will develop an Administrative Core for
effective communication and collaboration between the ARTI Center Project and Core Leaders and Co-Leaders
with National Cancer Institute (NCI) of Acquired Resis...

## Key facts

- **NIH application ID:** 10917376
- **Project number:** 5U54CA274220-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Boyi Gan
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,289,134
- **Award type:** 5
- **Project period:** 2022-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917376

## Citation

> US National Institutes of Health, RePORTER application 10917376, Acquired Resistance to Therapy and Iron (ARTI) Center (5U54CA274220-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10917376. Licensed CC0.

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