# Novel Pathogenic Roles and Mechanisms of Fibrinogen in Pancreatic Cancer

> **NIH VA I01** · MICHAEL E DEBAKEY VA MEDICAL CENTER · 2024 · —

## Abstract

The dismal prognosis associated with pancreatic ductal adenocarcinoma (PDAC) is attributed to the aggressive
nature of these tumors and the lack of effective screening or treatment strategies. PDAC is especially problematic
for the U.S. Veterans population, which has a higher PDAC prevalence than the general population. Studies
have shown that patients with PDAC have a high rate of venous thromboembolism (VTE), which is also an
important cancer-associated factor in the Veteran population. Critically, patients with VTE are more likely to have
an advanced stage of cancer and worse prognosis than patients without VTE. Fibrinogen is primarily considered
in the context of hemostasis; however, it is also important for other processes such as cell-cell interaction,
inflammation, and tumorigenesis. Although fibrinogen levels are elevated in cancer patient plasma and cancer
tissues, the mechanistic roles for fibrinogen in the pathogenesis of any cancer, including PDAC, are largely
unknown. We have performed extensive preliminary studies to show functional roles of fibrinogen in PDAC. For
the current project, we hypothesize that increased fibrinogen expression in the basal subtype of PDAC plays an
important role in cancer progression through the AKT/STAT3 signaling axis, thereby promoting EMT/metastasis,
chemoresistance and anti-apoptosis in cancer cells. We propose that a novel therapy (A2 protein) targeting
fibrinogen in combination with the first-line chemotherapeutic drug regimen (FOLFIRINOX) could be beneficial
primarily for PDAC patients with basal subtype tumors. Two specific aims are proposed: 1). Determine the
functions and molecular mechanisms of tumor-derived fibrinogen in the pathogenesis of the basal subtype of
PDAC in vitro and in vivo. 2). Determine the therapeutic efficacy of the novel combination of chemotherapy with
A2 protein targeting fibrinogen in the basal subtype of PDAC in PDX mouse models.
The proposed project is highly relevant to U.S. veterans due to their increased risk for PDAC. With the in depth
research on roles of tumor-derived and systemic fibrinogen on PDAC progression, and effective targeting
strategy, we expect this project to offer a new, groundbreaking paradigm for VA patient care, and bring a novel
treatment option for basal subtype of PDAC patients. Results obtained from the current project will be ready to
implement into clinical trials.

## Key facts

- **NIH application ID:** 10701436
- **Project number:** 1I01BX005806-01A2
- **Recipient organization:** MICHAEL E DEBAKEY VA MEDICAL CENTER
- **Principal Investigator:** Qizhi C. Yao
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10701436

## Citation

> US National Institutes of Health, RePORTER application 10701436, Novel Pathogenic Roles and Mechanisms of Fibrinogen in Pancreatic Cancer (1I01BX005806-01A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10701436. Licensed CC0.

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