# New Therapuetics for Pancreatic Cancer

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2022 · $600,834

## Abstract

SUMMARY
 Our proposal will develop the largest cohort of Adenosquamous cancer of the pancreas (ASCP) models
and characterize the genomic and epigenomic landscapes of this devastating tumor in comparison with that of
pancreatic ductal adenocarcinoma (PDAC), with the expectation of identifying epigenetic features that can be
exploited to selectively impair growth of cells of one or both subtypes. ASCP is a rare subtype of pancreatic
cancer representing 2-4% of all pancreatic cancers with an incidence rate of < 1 case per 100,000 people per
year. Strikingly, ASCP displays a higher metastatic potential and a worse clinical outcome than the more
common (90-95% of cases) PDAC. Yet, a large population-based analysis did not detect any differences in
tumor stage at the time of diagnosis between PDAC and ASCP. Despite aggressive surgical management for
those few patients who present with resectable disease, the median survival has been reported to be
consistently less than 1 year. Furthermore, no standard adjuvant therapy, or first line therapies for metastatic
patients, has been established for this aggressive subtype of pancreatic cancer. Our preliminary observations
suggest a unique ASCP genomic and epigenomic landscape and demonstrate how our molecular studies can
identify candidate therapeutic targets and strategies for this dismal cancer that we now aim to validate using
unique preclinical ASCP models. It is our HYPOTHESIS that ASCP evolve from the same lineage as PDACs
yet contain distinct epigenomic features driving the aggressive phenotype of ASCP. We propose that
modulating ASCP epigenome will sensitize ASCP cells to existing chemotherapies (e.g., gemcitabine and
irinotecan) used as first line of treatments for PDAC and other solid malignancies. Further, we will evaluate the
effects of depletion of key epigenetic proteins on the maintenance of the ASCP epigenome and cell viability,
and the impact of epigenetically targeted drugs in combination with chemotherapeutic agents on ASCP tumor
growth with the aim of identifying precision treatments for ASCP. Our studies will provide insight into the
epigenetic mechanisms that maintain the ASCP and PDAC phenotypes and will be relevant to squamous
carcinomas from other tissues (e.g., colon, lung and stomach). Further, the successful completion of this
proposal will serve as a foundation for new treatment options for ASCP patients and potentially other cancers
with mixed histologies.

## Key facts

- **NIH application ID:** 10465802
- **Project number:** 1R01CA265050-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Michael T Barrett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $600,834
- **Award type:** 1
- **Project period:** 2022-05-03 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465802

## Citation

> US National Institutes of Health, RePORTER application 10465802, New Therapuetics for Pancreatic Cancer (1R01CA265050-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10465802. Licensed CC0.

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