ArticleThe Journal of clinical investigation2011
EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 255 citations in OpenAlex.
- Targeted analysis of Ubiquitin-Specific Peptidase (USP8) in a population of Iranian people with Cushing's disease and a systematic review of the literature.BMC endocrine disorders · 2024Pooled it
- Trial
- The germline landscape of pituitary adenomas: established and emerging predisposition genes.The Journal of clinical endocrinology and metabolism · 2026Review
- Review
- Molecular biology of pituitary neuroendocrine tumors.Journal of neuro-oncology · 2026Review
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- Review
- Cushing's Disease in the Animal Kingdom: Translational Insights for Human Medicine.International journal of molecular sciences · 2025Review
- Management of Cushing's disease in the initial phase~From detection to surgery~.Endocrine journal · 2025Review
- Genetic models of Cushing's disease : From cells, in vivo transgenic models to human pituitary organoids.Pituitary · 2025Review
- Article
- New Trends in Treating Cushing's Disease.TouchREVIEWS in endocrinology · 2024Article
- Expression assays of selected lncRNAs in non-functioning pituitary adenomas.Discover oncology · 2024Article
- The biological behavior and clinical outcome of pituitary adenoma are affected by the microenvironment.CNS neuroscience & therapeutics · 2024Review
- Current and Emerging Pharmacological Therapies for Cushing's Disease.Current pharmaceutical design · 2024Review
- Review
- Article
- Article
- An individualized approach to the management of Cushing disease.Nature reviews. Endocrinology · 2023Review
- Review
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cushing disease is a condition in which the pituitary gland releases excessive adrenocorticotropic hormone (ACTH) as a result of an adenoma arising from the ACTH-secreting cells in the anterior pituitary. ACTH-secreting pituitary adenomas lead to hypercortisolemia and cause significant morbidity and mortality. Pituitary-directed medications are mostly ineffective, and new treatment options are needed. As these tumors express EGFR, we tested whether EGFR might provide a therapeutic target for Cushing disease. Here, we show that in surgically resected human and canine corticotroph cultured tumors, blocking EGFR suppressed expression of proopiomelanocortin (POMC), the ACTH precursor. In mouse corticotroph EGFR transfectants, ACTH secretion was enhanced, and EGF increased Pomc promoter activity, an effect that was dependent on MAPK. Blocking EGFR activity with gefitinib, an EGFR tyrosine kinase inhibitor, attenuated Pomc expression, inhibited corticotroph tumor cell proliferation, and induced apoptosis. As predominantly nuclear EGFR expression was observed in canine and human corticotroph tumors, we preferentially targeted EGFR to mouse corticotroph cell nuclei, which resulted in higher Pomc expression and ACTH secretion, both of which were inhibited by gefitinib. In athymic nude mice, EGFR overexpression enhanced the growth of explanted ACTH-secreting tumors and further elevated serum corticosterone levels. Gefitinib treatment decreased both tumor size and corticosterone levels; it also reversed signs of hypercortisolemia, including elevated glucose levels and excess omental fat. These results indicate that inhibiting EGFR signaling may be a novel strategy for treating Cushing disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.