# Development of a patient-derived tumoroid culture system to explore novel medical treatments for refractory prolactinomas > **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $218,790 ## Abstract ABSTRACT Prolactinomas (PRL-omas), the most common secreting pituitary tumors, frequently cause hypogonadism and subfertility. Although dopamine agonist therapy often works well initially and 1/3 of patients experience long-term remission after 2 years of therapy, 1/3 of patients require long-term D2 agonist therapy to maintain normal PRL levels and a further 1/3 of patients are either refractory to DA therapy or intolerant of their side effects. Although surgical resection can be offered in some, remission rates in large locally invasive tumors is <50%. Translational research has been hampered by the lack of any human PRL-oma cell models. Using current methodologies, human PRL-oma cultures only survive for 7-10 days in vitro. There is an urgent unmet need for establishment of a human PRL-secreting tumor model that retains its highly differentiated phenotype and allows sufficient long-term expandability of cells for use in preclinical translational research and development of novel treatment options. We compared the global transcriptome landscape in consecutive passages from two human prolactin-secreting pituitary tumor primary cultures using bulk RNA-seq to understand the molecular events leading to loss of hormone secretion during in vitro human prolactinoma culture. As pituitary tumor cells lost hormone secretion, we observed a reduction in angiogenesis, survival signals and immune responses in parallel with increased collagen catabolism, cell adhesion and extracellular matrix organization. Guided by these findings, we developed a unique 3-dimensional (3D) PRL-oma culture system and for the first time, we have generated long-term (> 6 months) expandible PRL-secreting 3D human pituitary tumor cultures (>6 months). In the first of two aims, we will use our unique patient-derived 3D PRL-oma culture model in a high throughput screen to identify small molecule inhibitors of PRL secretion and proliferation. We have already demonstrated the feasability of this approach and identified a compound of interest in a pilot screen and now wish to conduct an expanded HTS to identify novel therapies for patients with refractory PRL-omas. Our primary screen will include pharmacological validation and repurposing-, targeted-, lead-like- and diverse- libraries. Initial hits will be selected using robust z-score statistics and transitioned to aim 2 for further development. Aim 2 will employ a cascade of follow-up assays to validate potential hit compounds. These will include dose-response curves in both rat and human PRL-oma cells, assessment and exclusion of non-specific overly toxic compounds. And tests of specificity on hormone secretion in various murine and human neuroendocrine tumors. Additionally, in-silica target prediction will be combined with RNA-seq transcriptome profiling to segregate drug target pathways and deconvolute the MOA of resultant hits. Finally, potential actions of hits on identified pathway targets will be corroborated by pathway disru... ## Key facts - **NIH application ID:** 10643450 - **Project number:** 1R21CA264838-01A1 - **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES - **Principal Investigator:** ANTHONY P HEANEY - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2023 - **Award amount:** $218,790 - **Award type:** 1 - **Project period:** 2023-04-01 → 2025-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10643450 ## Citation > US National Institutes of Health, RePORTER application 10643450, Development of a patient-derived tumoroid culture system to explore novel medical treatments for refractory prolactinomas (1R21CA264838-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10643450. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*