# Tumor Subtypes and Therapy Response in Pancreatic Cancer

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $806,124

## Abstract

ABSTRACT
FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have emerged as the first-line treatments for
patients with pancreatic cancer (PDAC). These two regimens have not been compared in the first-line setting,
and treatment selection is guided by physician's “best-guess”. Matching the most effective systemic therapy with
the potential vulnerabilities of the tumor has been an unrealized hope for patients and a solid barrier to
personalized medicine for PDAC. We have identified molecular subtypes of PDAC that are robust and replicable.
We and others have found that basal subtype patients rarely respond to FFX, but show responses to GnP. Thus,
identifying patients at initial diagnosis to optimize treatment is critical. Proteomic analysis of tumor samples
shows differential kinase expression in basal tumors including previously known targets such as EGFR. Based
on our findings of subtype association with treatment response, we have developed a robust and replicable
single sample classifier PurIST assay that is now CLIA approved and ready. For this proposal, we will use CLIA
PurIST for treatment selection of either FFX or GnP (PANCREAS trial, PI Tsai). To determine if repurposing anti-
EGFR therapies specifically for basal tumor patients may be promising, we will analyze two completed clinical
trials. To identify additional options for patients, we will evaluate two ongoing clinical trials that include cisplatin
to GnP as well as paricalcitol and nivolumab. To develop alternative approaches and to overcome FOLFIRINOX
resistance, we will identify new targets for basal tumors using a tailored CRISPR screen. Finally, we will use our
deconvolution and single-cell methods to determine if the tumor and tumor microenvironment may be predictive
of response in the therapies studied.
Leveraging the strength of molecular subtyping expertise at the University of North Carolina at Chapel Hill and
the tremendous neoadjuvant therapy infrastructure Medical College of Wisconsin's Pancreatic Cancer Program,
we will conduct, to our knowledge, the first precision oncology trial in neoadjuvant PDAC patients. Results from
this trial may revolutionize precision oncology approaches such as PurIST for PDAC.

## Key facts

- **NIH application ID:** 10317796
- **Project number:** 2R01CA199064-06A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Susan Tsai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $806,124
- **Award type:** 2
- **Project period:** 2016-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317796

## Citation

> US National Institutes of Health, RePORTER application 10317796, Tumor Subtypes and Therapy Response in Pancreatic Cancer (2R01CA199064-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10317796. Licensed CC0.

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