# The Houston Center for Acquired Resistance Research (H-CARR)

> **NIH NIH U54** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $238,959

## Abstract

Overall SUMMARY
 Head and neck squamous cell carcinoma (HNSCC) remains a leading cause of cancer deaths worldwide
with ~500,000 cases/year. Cisplatin is the gold standard systemic agent for HNSCC. Cisplatin resistance, both
intrinsic and acquired, has been described in preclinical models and is frequently encountered in clinical practice;
when it occurs it is deadly. The overarching goal of H-CARR is to develop a robust biological understanding
of the key drivers of cisplatin resistance in HNSCC and develop the means of detecting it early in development
and overcoming it once it arises. We previously showed that: 1) cellular processing of cisplatin generated
metabolic stress is a critical driver of sensitivity and/or resistance and 2) coordinated genomic (TP53 mutation)
and transcriptomic (Nrf-2 activation) reprogramming is essential to organizing the metabolic response to cisplatin
generated stress. H-CARR brings together our biological and metabolic models of cisplatin resistance and our
translational capabilities to image tumor metabolism non-invasively and detect biological shifts using circulating
tumor cells (CTCs), to provide a comprehensive window into acquisition of cisplatin resistance as outlined in the
Projects listed below, supported by a robust administrative and analytical infrastructure organized into 3 Cores.
Project 1 will use state of the art metabolomic studies to identify the critical metabolic dependencies of
cisplatin resistant HNSCC, identify opportunities for effective metabolic inhibition and improve our understanding
of the cross-talk between the acquisition of cisplatin resistance and modulation of the tumor immune
microenvironment. Project 2 will explore the genomic and transcriptomic reprogramming required to sustain the
metabolic shifts which accompany development of resistance and interrogate how Nrf-2 dependent and
independent signaling drives resistance and enhanced distant metastasis through intrinsic cellular mechanisms
and paracrine signaling between tumor cells and adrenergic neurons. Project 3 will test whether the metabolic
reprogramming outlined in Project 1 is detectable via non-invasive imaging (hyperpolarized magnetic resonance
imaging) and whether the biological shifts outlined in Project 2 due to clonal extinction and expansion can be
detected using CTC analysis in patients undergoing cisplatin-based treatment.
 H-CARR has the potential to realize the full clinical utility of cisplatin by identifying acquisition of
resistance early during treatment and developing the means to overcome this and associated phenotypes such
as enhanced distant metastasis. Successful completion of the proposed experiments will generate the new
clinical standard for precision oncology approaches to clinical utilization of cisplatin in HNSCC and related upper-
aerodigestive tract cancers of the lung and esophagus and therefore have a major impact on cancer survival
worldwide.

## Key facts

- **NIH application ID:** 11010062
- **Project number:** 3U54CA274321-03S1
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Jeffrey Nicholas Myers
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $238,959
- **Award type:** 3
- **Project period:** 2022-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11010062

## Citation

> US National Institutes of Health, RePORTER application 11010062, The Houston Center for Acquired Resistance Research (H-CARR) (3U54CA274321-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11010062. Licensed CC0.

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