# Addressing biological and therapeutic gaps in rare neuroendocrine cancer with a novel organoid-based model

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $483,461

## Abstract

This proposal responds to the provocative question PQ9: What methods can be developed to effectively
study small or rare populations relevant to cancer research? We will address this question by generating
organoid models of pheochromocytomas and paragangliomas (PPGL) to fill gaps in the mechanisms underlying
tumor behavior and in therapeutic opportunities. PPGLs are rare catecholamine-secreting, neural crest-derived
tumors originating from adrenal or extra adrenal paraganglia, respectively. Malignant PPGLs can only be
recognized after detection of metastases, implying a late diagnosis. Approximately 30-40% of paragangliomas,
and 10-15% of pheochromocytomas can develop metastases. In addition, PPGLs are clinically heterogeneous,
can be recurrent and invasive, even without metastasis, but predictors of clinical behavior are lacking. Treatment
options are currently limited, with modest effects on survival, and advances in this area are dampened by a
scarcity of research models. Therefore, there is a critical need for developing models to uncover biological
mechanisms that facilitate clinical outcome prediction and reveal molecular vulnerabilities which can be explored
for therapeutic purposes. Our preliminary data indicate that we can successfully generate PPGL organoids that
are amenable for drug screen. Our aims are: 1) to determine if PPGL organoids recapitulate features of the
parental tumor; 2) to leverage PPGL organoids to investigate outstanding biological questions, including the
existence of cell subtypes that may be related to tumor outcome, and 3) to utilize PPGL organoids for high-
throughput drug screening that uncover vulnerabilities for future therapeutic testing, including novel leads
suggested in our preliminary data. The proposed project will serve as a useful resource for designing future
studies to decode the cellular and molecular mechanisms underlying PPGL development and clinical
heterogeneity. Results from these studies may provide the groundwork for future testing of candidate drugs that
might have immediate clinical application.

## Key facts

- **NIH application ID:** 10485252
- **Project number:** 5R01CA264248-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** PATRICIA Leal DAHIA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $483,461
- **Award type:** 5
- **Project period:** 2021-09-08 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485252

## Citation

> US National Institutes of Health, RePORTER application 10485252, Addressing biological and therapeutic gaps in rare neuroendocrine cancer with a novel organoid-based model (5R01CA264248-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10485252. Licensed CC0.

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