# Repurposing Bazedoxifene for chemoprevention in pre-invasive pancreatic cancer IPMN

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $238,542

## Abstract

PROJECT SUMMARY/ABSTRACT
Precancerous lesions of pancreatic ductal adenocarcinoma (PDAC) called pancreatic intraductal papillary
mucinous neoplasms (IPMN) can be detected radiographically, but monitoring and identifying patients who can
benefit from surgical intervention before the development of malignant tumor has been an immense challenge
in the management of patients with IPMN. Here we propose to investigate the feasibility of repurposing FDA-
approved Bazedoxifene as a chemopreventive therapy for patients with IPMN in preclinical models, which may
complement and improve the current care for these patients who are at high-risk for developing PDAC.
Using unbiased computational and chemical screens, we have previously identified Bazedoxifene as a novel
IL-6 signaling antagonist that can directly bind to GP130, a common component of IL-6 receptor complex. IL-
6/STAT3 is a vital oncogenic signaling axis that promotes pancreatic tumorigenesis. Elevated IL-6 level is
associated with inflammation, aging, and poor prognosis and metastasis in pancreatic cancer patients. More
recently, IL-6 secretion stimulated by IL-1-NFkB-JAK/STAT signaling is implicated in activating tumor-
promoting inflammatory cancer associated fibroblast cells (iCAF). While inhibition of IL-6 and STAT3 to
suppress PDAC has been pursued previously, here we propose to explore the uncharted efficacy of
Bazedoxifene (a well-tolerated FDA-approved medication that is prescribed for osteoporosis prevention and
can be taken orally) as a chemopreventive measure for patients who are identified as high-risk for developing
PDAC, specifically those with detectable premalignant IPMN.
To test our novel hypothesis that repurposing Bazedoxifene for chemoprevention would block IPMN
progression to PDAC via inhibition of IL-6 signaling, we will 1) use 3D organoids derived from our unique
mouse model for IPMN and from surgically resected IPMNs from patients to evaluate the functional and
molecular impacts of Bazedoxifene as a chemopreventive agent on epithelial cells (Aim 1); 2) use our IPMN
mouse model and orthotopically implanted murine and human IPMN 3D organoids to investigate the efficacy of
Bazedoxifene as a chemopreventive therapy in vivo (Aims 1 & 2); 3) to investigate if Bazedoxifene also affects
the stromal components, specifically the activation of quiescent fibroblast cells and the interconvertibility
between CAF subtypes in vitro and in vivo (Aims 1 & 2). And lastly 4) since our knowledge of IL-6, metabolic
alterations, CAF subtypes in pancreatic tumorigenesis has been gathered majorly from premalignant PanIN
and invasive PDAC, to address this gap in knowledge, we will also compare and contrast IPMN organoids with
PanIN and PDAC organoids to advance our understanding of the understudied IPMN (Aims 1 & 2).
The success of our application will be transformative to clinical care of patients with IPMN and may be
applicable to other known high-risk groups (i.e. patients with chronic pancreati...

## Key facts

- **NIH application ID:** 10363411
- **Project number:** 1R21CA259715-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Christine Iok In Chio
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $238,542
- **Award type:** 1
- **Project period:** 2021-12-14 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10363411

## Citation

> US National Institutes of Health, RePORTER application 10363411, Repurposing Bazedoxifene for chemoprevention in pre-invasive pancreatic cancer IPMN (1R21CA259715-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10363411. Licensed CC0.

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