# Research Project 1 PDAC Molecular Subtypes Contribute to Cancer Health Disparities

> **NIH NIH U54** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $187,428

## Abstract

PROJECT SUMMARY
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is refractory to current treatment strategies
due in part to adaptive mechanisms of chemoresistance. Racial health disparities also confound the treatment
and care of these patients. Blacks have significantly higher incidence rates of PDAC and decreased survival
times compared to Whites and Latino/Hispanics (L/H) even after socioeconomic status and tumor stages are
controlled. Therefore, it is likely different racial groups exhibit unique molecular characteristics in PDAC tumors
that contribute to these health disparities. The molecular characteristics that distinguish PDAC tumors between
racial groups have the potential to identify novel therapeutic targets required to overcome the disparities. Indeed,
delineating the underlying molecular basis for health disparities in lung, breast and prostate cancers has led to
therapeutic advancements and improved patient outcomes. Similar breakthroughs for PDAC are possible and
needed for this deadly disease, but this field of research has not yet been adequately explored. We identified 4
distinct subtypes of PDAC (Metabolic, Progenitor-like, Proliferative, and Inflammatory) that can be distinguished
using multivariate analysis of quantitative mass spectrometry data. These PDAC subtypes are predictive of
therapeutic response, but this has not yet been analyzed in a racially diverse population. We have examined the
proteomes of primary PDAC tumors using quantitative mass spectrometry and identified unique protein
signatures for Blacks, L/H, and Whites. In PDAC tumors from Black patients, we observed features consistent
with the Inflammatory subtype of PDAC, which is characterized by an inflammatory microenvironment and
resistance to chemotherapy. Therefore, it is possible that race influences subtype and Blacks could preferentially
develop the more aggressive and treatment refractory Inflammatory subtype. Therefore, strategies are needed
to modulate subtype to improve response to chemotherapy. Toward this goal, our proteomic analysis also
identified that the polycomb repressor complex 1 protein RNF2 is upregulated in PDACs from Blacks compared
to Whites. We have also discovered that RNF2 regulates mRNA expression of the PDAC subtype specification
factor GATA6 and inhibiting RNF2 promotes a molecular shift toward the more chemosensitive Classical subtype
of PDAC. In general terms, the Specific Aims in this proposal are designed to: 1) Determine the interaction
between race and PDAC subtype development in PDX models; 2) Determine the impact of RNF2 on EZH2
regulation of GATA6 and in diverse PDAC PDX models; and 3) To quantify the response of PDAC PDX to select
NCI-IND compounds targeting epigenetic modifiers. The successful completion of these aims has the potential
to mitigate racial health disparities in PDAC and broadly improve overall patient survival by optimizing precision
therapeutic strategies.

## Key facts

- **NIH application ID:** 10890850
- **Project number:** 5U54CA283762-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Nicholas Taylor Woods
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $187,428
- **Award type:** 5
- **Project period:** 2023-07-19 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890850

## Citation

> US National Institutes of Health, RePORTER application 10890850, Research Project 1 PDAC Molecular Subtypes Contribute to Cancer Health Disparities (5U54CA283762-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10890850. Licensed CC0.

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