# Identifying Actionable Signatures of Duodenopancreatic Neuroendocrine Tumor Progression in MEN1

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $416,543

## Abstract

Project summary
 Patients with Multiple Endocrine Neoplasia type 1 (MEN1) almost invariably develop multiple
duodenopancreatic neuroendocrine tumors (dpNETs), but only a subset progress to metastasis. Currently, we
lack the ability to identify those patients at high risk of developing aggressive and metastatic disease. Surgical
resection is the only curative option when dpNETs are localized, and is associated with significant morbidity.
There is a critical unmet need for molecular, actionable features associated with the development of metastatic
dpNETs that provide for markers of risk stratification, or represent therapeutic targets. Our long-term goals are
to develop a liquid biopsy approach to identify patients with MEN1-related dpNETs that are at high risk of
developing distant metastasis and to develop novel targeted therapies to prevent metastasis. The overall
objective of this study is to identify actionable signatures of pNET progression by performing integrated multi-
omic profiling of longitudinally collected plasma-, plasma-derived exosomes and tissue from a mouse model of
MEN1-pNET and of retrospective blood samples from patients with MEN1-related dpNETs. To address this
objective, we propose two specific aims. In Specific Aim 1 we will collect longitudinal plasma, plasma-derived
exosomes, and tissue samples from a Men1fl/flPdx1-CreTg mouse model of MEN1-pNET and, using these
biospecimen, perform mass spectrometry based metabolomic, proteomic and immune complex profiling to
identify signatures associated with disease development and progression. In Specific Aim 2 we will identify blood-
based signatures associated with metastatic disease in human samples of MEN1-related dpNET. This will be
accomplished by untargeted metabolomic, proteomic and immune complex profiling of blood in a retrospective
cohort of MEN1 patients with dpNETs with distant metastases (cases; n=15); MEN1 patients with dpNETs
without distant metastases (n=30), and MEN1 patients without dpNETs (n=15). Blinded validation of identified
biomarkers will be performed in a second equally sized independent patient cohort.
 This unique collaboration takes advantage of state-of-the-art mass spectrometry technology, a disease
relevant genetic mouse model of MEN1-related pNET as well as blood samples from three well-characterized
MEN1 cohorts from expert centers in the US and Europe with the sole objective of identifying actionable features
that may offer utility for risk stratification or provide therapeutic targets. This project is significant because it aims
to address an unmet clinical need by identifying blood-based biomarkers associated with disease progression
and metastasis in patients with MEN1-related dpNETs as well as identifying a set of tumor antigens associated
with dpNETs that may be harnessed for the subsequent development of vaccines for subjects at risk and/or as
targets for immunotherapeutic applications. This approach opens new horizons for risk-stratificatio...

## Key facts

- **NIH application ID:** 10041298
- **Project number:** 1R21CA252426-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** SAMIR M HANASH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $416,543
- **Award type:** 1
- **Project period:** 2020-07-10 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041298

## Citation

> US National Institutes of Health, RePORTER application 10041298, Identifying Actionable Signatures of Duodenopancreatic Neuroendocrine Tumor Progression in MEN1 (1R21CA252426-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10041298. Licensed CC0.

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