The National Biorepository and Resource for Pituitary Neuroendocrine Tumor Translational Research (BioPitNeT)

PROJECT SUMMARY Pituitary neuroendocrine tumors (PitNETs) are rare and understudied heterogeneous tumors that are detrimental to health causing increased mortality and poor quality of life. Cushing’s disease (CD) is a serious endocrine disease caused by an adrenocorticotropic hormone (ACTH)-secreting PitNET that subsequently stimulates the

adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has several detrimental effects on health, including increased stroke rates, diabetes, obesity, depression, anxiety, and a threefold increase in the risk of death from cardiovascular disease and cancer. Despite decades of research, current treatments for CD

remain suboptimal, and the development of targeted therapies is challenging due to the limited knowledge of PitNET tumor cellular and molecular complexity. The RC2 will fund the National Biorepository and Resource for Pituitary Neuroendocrine Tumor Translational Research (BioPitNeT) which will be an open source,

clinically relevant deep tumor phenotyping platform and biorepository. This is the first phase of a contin- uum of translational- and hypothesis-driven research that will accelerate the development of effective therapies for PitNETs, preventing tumor recurrences and improving remission rates and quality of life for patients. The

BioPitNeT team will: 1) establish a large-scale unique resource within an infrastructure that will generate sus- tainable novel research tools benefiting investigators with focused translational research of PitNETs, and 2) implement interdisciplinary approaches and expertise to generate a resource that will foster translational and

hypothesis-driven research in PitNET diseases. The Registry for Adenomas of the PItuitary and related Disor- ders (RAPID) is a twelve center US consortium founded in 2021 to improve treatment of patients with PitNETs and funded by grateful patients. The BioPitNet leverages the RAPID Consortium clinical platform to combine

clinical annotations of future prospectively enrolled patients with molecular and pathological information using state-of-the-art preclinical models. The low incidence of CD requires multicenter collaboration and interdiscipli- nary team science partnerships between basic- and clinician-translational scientists comprising the expertise of

professionals trained in complimentary fields including medical and surgical treatment, neuropathology, molec- ular genetics of PitNETs, molecular pathology and high-plex spatial imaging, organoid and iPSC technology, canine comparative oncology disease models and translational bioinformatics. The BioPitNeT will be estab-

lished by the successful completion of Aim 1: To establish the BioPitNeT centralized biorepository comprising of resources that will be benchmarked to the patients’ PitNET tissue of origin, Aim 2: To develop a PitNET clinically relevant classification system for CD, and Aim 3: To establish a biobank of induced pluripotent stem

cell (iPSCs) lines genetically engineered to model corticotroph subtype PitNETs as a resource for investigating genetic underlying mechanisms of CD.