# Targeting CXCR2 axis in Pancreatic Cancer

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $402,559

## Abstract

Abstract
 Pancreatic cancer (PC) is the fourth leading causes of cancer-related deaths in both men and women and
is one of the most lethal malignancies with a 5-year survival rate of ~8% and median survival duration of fewer
than six months. Our long-term goal is that an understanding of the cellular and molecular mechanism(s) of the
metastatic phenotype and pro-inflammatory/pro-angiogenic tumor milieu and its judicious manipulation can
improve the treatment outcomes for PC patients. PC is frequently associated with oncogenic K-ras mutations
(90-95%). Our preliminary data and published reports suggest that CXCR2 and its ligands regulate the
behavior of tumor cells and recruitment of leukocytes, and endothelial (ECs) precursor cells. Limited literature
exists on the role of Kras-driven CXCR2-dependent signaling in the de novo pathogenesis of PC. Thus,
molecules driving a tumor-associated pro-inflammatory and pro-angiogenic phenotype have considerable
potential as therapeutic targets, yet this area remains relatively under-explored in PC. To our knowledge, very
little is known about the role of K-ras-driven CXCR2-dependent de novo PC development and impact of
CXCR2 targeting in pancreatic cancer progression and metastasis. Our central hypothesis is that oncogenic
Kras-induced expression of CXCR2 ligands plays a critical pro-tumorigenic role in inflammation-driven
spontaneous tumorigenesis, angiogenesis and metastasis. A corollary to this hypothesis is that CXCR2 and
its ligands are potential novel anti-tumorigenic and anti-metastatic therapeutic targets in PC. We will explore
the role of CXCR2 and its ligands using xenogenic transplant models and autochthonous animal models (K-
ras-driven) in PC pathology and develop a novel therapeutic strategy. To test our hypothesis, we will: 1) Define
the mechanism by which K-ras-induced CXCR2 ligands expression promotes tumorigenesis and recruit pro-
inflammatory and angiogenesis promoting precursor cells; and 2) Assess the therapeutic efficacy of targeting
CXCR2-mediated mechanisms in pancreatic cancer treatment. Together, these studies will provide a
mechanism for K-ras-dependent expression of CXCR2 ligands, delineate their role in PC pathobiology and
assess their potential as therapeutic targets. With pharmacologic inhibitors of CXCR2 already in clinical trials
for the treatment of inflammatory disorders, the rapid development of innovative cancer therapies targeting
CXCR2 in combination with conventional anti-tumor regimens is a highly attractive option for making inroads in
lethal PC.
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## Key facts

- **NIH application ID:** 9853766
- **Project number:** 5R01CA228524-03
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Surinder K. Batra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,559
- **Award type:** 5
- **Project period:** 2018-03-06 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853766

## Citation

> US National Institutes of Health, RePORTER application 9853766, Targeting CXCR2 axis in Pancreatic Cancer (5R01CA228524-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853766. Licensed CC0.

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