{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:42:28Z","timestamp":1785760948816,"version":"3.56.0"},"reference-count":66,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T00:00:00Z","timestamp":1666483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Cellular and Molecular Medicine (University of Arizona College of Medicine) startup funds (Zavros)","award":["P30 CA023074"],"award-info":[{"award-number":["P30 CA023074"]}]},{"name":"National Cancer Institute of the National Institutes of Health","award":["P30 CA023074"],"award-info":[{"award-number":["P30 CA023074"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>(1) Background: Cushing\u2019s disease (CD) is a serious endocrine disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumor (PitNET) that stimulates the adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has detrimental effects on health, including increased stroke rates, diabetes, obesity, cognitive impairment, anxiety, depression, and death. The first-line treatment for CD is pituitary surgery. Current surgical remission rates reported in only 56% of patients depending on several criteria. The lack of specificity, poor tolerability, and low efficacy of the subsequent second-line medical therapies make CD a medical therapeutic challenge. One major limitation that hinders the development of specific medical therapies is the lack of relevant human model systems that recapitulate the cellular composition of PitNET microenvironment. (2) Methods: human pituitary tumor tissue was harvested during transsphenoidal surgery from CD patients to generate organoids (hPITOs). (3) Results: hPITOs generated from corticotroph, lactotroph, gonadotroph, and somatotroph tumors exhibited morphological diversity among the organoid lines between individual patients and amongst subtypes. The similarity in cell lineages between the organoid line and the patient\u2019s tumor was validated by comparing the neuropathology report to the expression pattern of PitNET specific markers, using spectral flow cytometry and exome sequencing. A high-throughput drug screen demonstrated patient-specific drug responses of hPITOs amongst each tumor subtype. Generation of induced pluripotent stem cells (iPSCs) from a CD patient carrying germline mutation CDH23 exhibited dysregulated cell lineage commitment. (4) Conclusions: The human pituitary neuroendocrine tumor organoids represent a novel approach in how we model complex pathologies in CD patients, which will enable effective personalized medicine for these patients.<\/jats:p>","DOI":"10.3390\/cells11213344","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T20:43:50Z","timestamp":1666557830000},"page":"3344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Development of Human Pituitary Neuroendocrine Tumor Organoids to Facilitate Effective Targeted Treatments of Cushing\u2019s Disease"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-4657","authenticated-orcid":false,"given":"Jayati","family":"Chakrabarti","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85721, USA"},{"name":"Center for Biomedical Informatics and Biostatistics, University of Arizona Health Sciences, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared M.","family":"Churko","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Eschbacher","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2147-3478","authenticated-orcid":false,"given":"Saptarshi","family":"Mallick","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Arizona Cancer Center Bioinformatics Core, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Hermes","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palash","family":"Mallick","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2061-9428","authenticated-orcid":false,"given":"Ben N.","family":"Stansfield","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin W.","family":"Pond","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis A.","family":"Thorne","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C. J.","family":"Yuen","sequence":"additional","affiliation":[{"name":"Department of Neuroendocrinology, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Little","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Zavros","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,23]]},"reference":[{"key":"ref_1","first-page":"539","article-title":"Posterior Pituitary Activity from an Anatomical Standpoint","volume":"9","author":"Cushing","year":"1933","journal-title":"Am. J. 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