DeCure for Growth hormone secreting pituitary adenoma 1
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for growth hormone secreting pituitary adenoma 1 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGrowth hormone secreting pituitary adenoma 1 maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for growth hormone secreting pituitary adenoma 1 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
AHR interacting HSP90 co-chaperone (AIP) — AIP is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet moodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8QMO · 2.76 Å · ligand MOLYBDATE ION (MOO). Experimental structure, not a prediction.
What the evidence adds up to
Growth hormone secreting pituitary adenomas account for about 20% of all pituitary adenomas. Histopathological subtypes include pure GH cell adenomas (densely and sparsely granulated), mixed GH and prolactin cell adenomas, and monomorphous adenomas with primitive cells capable of secreting both hormones. Alterations in the cAMP pathway are molecular hallmarks of most GH-secreting adenomas, but these alterations do not confer specific phenotypes. A crucial role for ERK1/2 downstream of cAMP pathway alterations has been postulated based on human somatotroph adenoma cells in primary culture and murine somatotroph cell lines, but no single protein alteration has been assigned to one specific adenoma type.
In a retrospective study of 73 patients treated between 1990 and 2009, 12 had growth hormone secreting adenomas. Median tumour size was 3 cm, and most patients received postoperative radiotherapy at a median dose of 45 Gy. After a median follow-up of 8 years, hormone normalization rate for all secreting tumours was 55% (16 of 29 patients). The 10-year tumour control rate for secreting adenomas was 58%, compared to 100% for non-secreting adenomas. Progression free survival at 10 years was 98%, with only one endocrinological recurrence. Following surgery, 60% of patients suffered from pituitary function deficit. Late complications from radiotherapy were limited to one patient who developed cataract.
Surgery is usually the treatment of choice for acromegaly, but the evidence from the 2016 study shows that even with adjuvant radiotherapy, hormone normalization occurs in just over half of secreting tumour patients, and tumour control at 10 years is substantially worse for secreting adenomas than for non-secreting ones. The 2003 review notes that several new treatment methods have been developed, but does not provide efficacy data for any specific drug.
What remains missing are prospective trials that stratify patients by adenoma subtype and molecular alteration, particularly the Gsalpha and ERK1/2 pathway status, to determine whether these markers predict response to any intervention. The long-term endocrine consequences of surgery and radiotherapy are substantial, and no drug-based alternative has been shown in these abstracts to improve upon the 55% hormone normalization rate or the 58% 10-year tumour control.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurosurgical FOCUS · 2010 · 90 citations
Growth hormone-secreting adenomas: pathology and cell biology
AbstractThe majority of patients with acromegaly harbor a functioning growth hormone (GH) pituitary adenoma. Growth hormone–secreting adenomas correspond to about 20% of all pituitary adenomas. From the histopathological point of view, a variety of adenomas may present with clinical signs and symptoms of GH hypersecretion including pure GH cell adenomas (densely and sparsely granulated GH adenomas), mixed GH and prolactin cell adenomas, and monomorphous adenomas with primitive cells able to secrete GH and prolactin including the acidophilic stem cell adenoma and the mammosomatotroph cell adenoma. In this article, the author reviews the main pathological features of the GH-secreting adenomas and some of the molecular genetics mechanisms involved in their pathogenesis.
Journal of Neuroendocrinology · 2009 · 35 citations
Signalling Pathway Alterations in Pituitary Adenomas: Involvement of Gsα, cAMP and Mitogen‐Activated Protein Kinases
AbstractDespite extensive research on sporadic pituitary adenomas, it is not yet possible to assign one protein alteration to one specific type of pituitary adenomas. Nevertheless, alterations of the cAMP pathway appear to be molecular hallmarks of most growth hormone (GH)-secreting adenomas. However, these alterations do not confer specific phenotypes to patients carrying these alterations. In this review, we summarise the literature regarding signalling alterations observed in GH-secreting adenomas. We focus on Gsalpha alterations and their possible cross-talk with the extracellular signal-related kinase (ERK)1/2 pathway. In the light of results obtained on human somatotroph adenoma cells in primary culture and on models of murine somatotroph cell lines, we postulate a crucial role for ERK1/2 in GH-secreting adenomas downstream of cAMP pathway alterations that might impact the tumoural phenotype.
Long-term outcomes of surgery and radiotherapy for secreting and non-secreting pituitary adenoma
AbstractPURPOSE: To investigate treatment outcome and long term complication after surgery and radiotherapy (RT) for pituitary adenoma. MATERIALS AND METHODS: From 1990 to 2009, 73 patients with surgery and RT for pituitary adenoma were analyzed in this study. Median age was 51 years (range, 25 to 71 years). Median tumor size was 3 cm (range, 1 to 5 cm) with suprasellar (n = 21), cavernous sinus extension (n = 14) or both (n = 5). Hormone secreting tumor was diagnosed in 29 patients; 16 patients with prolactin, 12 patients with growth hormone, and 1 patient with adrenocorticotrophic hormone. Impairment of visual acuity or visual field was presented in 33 patients at first diagnosis. Most patients (n = 64) received RT as postoperative adjuvant setting. Median RT dose was 45 Gy (range, 45 to 59.4 Gy). RESULTS: Median follow-up duration was 8 years (range, 3 to 22 years). In secreting tumors, hormone normalization rate was 55% (16 of 29 patients). For 25 patients with evaluable visual field and visual acuity test, 21 patients (84%) showed improvement of visual disturbance after treatment. The 10-year tumor control rate for non-secreting and secreting adenoma was 100% and 58%, respectively (p < 0.001). Progression free survival rate at 10 years was 98%. Only 1 patient experienced endocrinological recurrence. Following surgery, 60% (n = 44) suffered from pituitary function deficit. Late complication associated with RT was only 1 patient, who developed cataract. CONCLUSION: Surgery and RT are very effective and safe in hormonal and tumor growth control for secreting and non-secreting pituitary adenoma.
Postgraduate Medical Journal · 2003 · 18 citations · open access
Modern treatment of acromegaly
AbstractAcromegaly is an endocrine disorder characterised by increased morbidity and mortality. It is usually caused by a growth hormone secreting pituitary adenoma and is manifested by a variety of clinical features. Surgery is usually the treatment of choice, however over the last few years, several new methods of treatment have been developed. A recent consensus on the targets for treatment has led to multiple studies being conducted to assess the efficacy of the currently available options. This review examines the evidence for and against these treatments.
Frontiers in Surgery · 2016 · 6 citations · open access
Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms
AbstractThe current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.
Neuroscience Discovery · 2014 · 2 citations · open access
Gamma knife surgery in management of secretory pituitary adenoma preliminary evaluation of role, efficacy and safety
AbstractIntroduction Pituitary adenomas are common lesions and represent 20% of all primary brain tumors [1-3]. Pituitary adenomas are classified into two groups. The first is the secretory pituitary adenoma that produce excess of normal pituitary hormones usually they are microadenoma. Such functioning adenomas include those with Cushing's disease (high adernocorotitrophic hormone-ACTH,
International Journal of Endocrine Oncology · 2016 · 2 citations
Epidemiological Variations of Aggressive Growth Hormone-Secreting Adenomas
AbstractAcromegaly is a chronic disorder characterized by increased morbidity and mortality in uncontrolled patients. Growth hormone-secreting pituitary adenoma is the hallmark in the majority of cases, generally considered as benign due to lack of distant metastases. However, clinical behavior in a certain proportion of these adenomas could be quite aggressive, causing difficulties in their management. Aggressive pituitary adenomas have some clinical, radiological, ultrastructural and molecular features in common and they are usually resistant to the standard treatment. In the recent years, efforts have been made to define the most appropriate markers of such adenomas that would allow an early detection and efficient individualized therapeutic strategy. The aim of this review is to give an update on epidemiology and certain markers predicting aggressive behavior of somatotropinomas.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
