# Development and Standardization of a Novel Pituitary Adenoma Organoid Model for the Study and Treatment of Cushing's Disease

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2024 · $302,700

## Abstract

PROJECT SUMMARY/ABSTRACT
Cushing’s disease (CD) is a serious endocrine disorder characterized by an adrenocorticotropic hormone
(ACTH)-secreting PitNET that subsequently stimulates the adrenal glands to overproduce cortisol. Chronic
exposure to excess cortisol has wide ranging and detrimental effects on health, including increased stroke rates,
diabetes, obesity, depression, anxiety and death. Although CD is linked to a threefold increase in the risk of
death, the advancement of current standard of care medical therapy is lacking. Current treatments exhibit low
efficacy and tolerability for patients. The absence of preclinical models that replicate the complexity of the
adenoma tissue has prevented us from developing effective therapies that are targeted to the tumor directly. The
first-line treatment for CD is pituitary surgery. In the hands of an experienced surgeon, tumor recurrence occurs
in as many as 30% to 50% of patients during the 10-year follow-up period. Despite multiple treatments,
biochemical control is not achieved in approximately 50% of patients, suggesting that in routine clinical practice,
initial and long-term disease remission is not achieved in a substantial number of CD patients . Hence, medical
therapy is often considered in the following situations: when surgery is contraindicated or fails to achieve
remission, or when recurrence occurs after apparent surgical remission. While stereotactic radiosurgery treats
incompletely resected or recurrent PitNETs, the main drawbacks include the longer time to remission and the
risk of hypopituitarism. There is an inverse relationship between disease duration and reversibility of
complications associated with CD, thus emphasizing the importance of targeting the pituitary adenoma early.
The primary barrier to developing new medical therapies is the lack of human relevant advanced in vitro tumor
models. Pituitary cell lines do not reproduce the multicellular complexity of PitNETs. In this instance, the overall
objective is to develop PitNET organoids to advance our understanding of the pathogenesis and treatment of
pituitary tumors in CD patients. The overall goal will be successfully achieved by collaborative efforts between
the University of Arizona (UA) and Barrow Neurological Institute (BNI) that will leverage the expertise of
professionals trained in complimentary fields including surgical treatments, pathology and cell biology of pituitary
disease, organoid technology and high throughput data analysis including dug screening, molecular profiling,
and transcriptomics. This led us to develop Specific Aims: 1) To use human PitNET derived organoids to define
the molecular signatures of corticotroph tumor subtypes in CD, and 2) To use the pituitary tumor organoids as a
preclinical model to accelerate targeted therapies for patients with CD. At the completion of the funding period,
we will be positioned to implement patient-relevant organoids to accelerate the development of therapies th...

## Key facts

- **NIH application ID:** 10847469
- **Project number:** 5R01DK133325-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Andrew Scott Little
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $302,700
- **Award type:** 5
- **Project period:** 2023-05-25 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847469

## Citation

> US National Institutes of Health, RePORTER application 10847469, Development and Standardization of a Novel Pituitary Adenoma Organoid Model for the Study and Treatment of Cushing's Disease (5R01DK133325-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10847469. Licensed CC0.

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