# Tumor subtypes and therapy response in pancreatic cancer

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $824,656

## Abstract

Abstract
We have identified two novel tumor-specific subtypes of pancreatic cancer which we call “classical” and “basal-
like”. Several findings illustrate the power of our findings. Our subtypes were not only prognostic in our own
dataset but also independently validated the presence and prognostic significance of our subtypes in the
recently published International Cancer Genome Consortium (ICGC) PDAC microarray dataset as well as the
unpublished publically available data from The Cancer Genome Atlas (TCGA). Importantly, genes from the
“basal-like” factor, including laminins and keratins, were also consistent with basal subtypes previously defined
in bladder and breast cancers, leading us to hypothesize that like both these cancers basal subtypes although
more aggressive, are conversely more sensitive to cytotoxic therapies. We have also found that both
genetically engineered mouse models and cell lines inadequately represent our classical subtype with only
patient-derived xenograft (PDX) tumors showing representation of both. Finally we have also confirmed and
strengthened our previous association between kinome activation profiles since our initial submission. Our two
subtypes suggesting that novel kinase inhibitor approaches may be tailored to each subtype. Thus we will use
novel proteomic approaches to assess the baseline activation state of the kinome in each of our subtypes and
use PDX models to determine whether our subtypes are associated with response to novel kinases inhibitor
and cytotoxic therapies. Furthermore to advance the translation of our findings we propose to begin to evaluate
the association of our subtypes with treatment response in existing deidentified patient samples from two
different institutions (Dana-Farber Cancer Institute and Indiana University).

## Key facts

- **NIH application ID:** 9983613
- **Project number:** 5R01CA199064-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Lee M Graves
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $824,656
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983613

## Citation

> US National Institutes of Health, RePORTER application 9983613, Tumor subtypes and therapy response in pancreatic cancer (5R01CA199064-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9983613. Licensed CC0.

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