DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for adenoma — screening already-approved drugs against its 15-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAdenoma maps to a 15-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 adenoma 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
dihydrofolate reductase (DHFR) — DHFR 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4M6J · 1.201 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
In a series of 490 transsphenoidal surgeries for Cushing’s disease performed between 1993 and 2004, 111 cases had no histological confirmation of an ACTH-staining adenoma. Among these patients, 50% achieved remission, compared with 79% for the entire series and 88% for patients with a confirmed adenoma. The recurrence rate among those who did remit was 21% (seven of 33 evaluated), with three of those recurrences occurring between two and four months after remission. Patients who had undergone two prior transsphenoidal surgeries had lower remission rates than those with fewer prior surgeries.
Among 237 patients with non-functioning pituitary adenomas that regrew after primary treatment at two UK centres, the five-year rate of a second regrowth was 35.3% overall. This rate varied by management: 36.2% after surgery alone, 12.5% after radiotherapy alone, 12.7% after surgery combined with radiotherapy, and 63.4% with monitoring alone. Of those managed by monitoring, 34.8% eventually required intervention. Among patients who had a second regrowth, the five-year rate of a third regrowth was 26.4% overall, with rates of 24.4% after surgery, 0.0% after radiotherapy or surgery plus radiotherapy, and 48.3% with monitoring. Malignant transformation occurred in two of 237 patients. A separate single-institute study followed 434 patients with non-functioning pituitary adenomas to establish their natural history, but no quantitative outcomes from that cohort are reported in the abstract.
A 2024 study of endoscopic transsphenoidal surgery for functional pituitary adenomas compared two resection techniques. Among 46 patients (23 with acromegaly and 13 with Cushing’s disease), 26 underwent piecemeal resection and 10 underwent complete pseudocapsule resection. Remission was achieved in 80% of the pseudocapsule group versus 57.7% of the piecemeal group. No carotid artery injury, epistaxis, intracranial infection, or loss of olfaction occurred in either group; one patient in the pseudocapsule group had transient vision loss. The authors note the small number of cases and early experience.
What remains missing is prospective data on which patients without histological confirmation of adenoma might still benefit from repeat surgery versus alternative treatments, and whether pseudocapsule-based resection can be replicated in larger, multicentre trials with longer follow-up. The natural history of non-functioning adenomas remains incompletely characterised, and no trial has yet stratified patients by molecular markers or imaging features to predict which regrowths will require intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Clinical Endocrinology & Metabolism · 2007 · 103 citations · open access
Outcomes and Management of Patients with Cushing’s Disease without Pathological Confirmation of Tumor Resection after Transsphenoidal Surgery
AbstractCONTEXT: Despite the success of transsphenoidal surgery (TSS) for the treatment of Cushing's disease, in a number of cases, an ACTH-staining pituitary adenoma is not identified histologically. The clinical significance of lack of histological confirmation remains unclear. SETTING: This was a retrospective review of patients treated at the University of Virginia Medical Center. PATIENTS: Of 490 TSS procedures for Cushing's disease between 1993 and 2004, we identified 111 cases without histological adenoma confirmation. MAIN OUTCOME MEASURE: Remission and recurrence of Cushing's disease were measured. RESULTS: Overall, 50% of these patients achieved remission, a figure lower than for our entire series (79%) and for patients with histological confirmation of an ACTH-staining adenoma (88%) (P < 0.001). Patients with a history of two prior TSS achieved remission less often than patients with a history of fewer TSS (P = 0.026). No other factors influenced remission rates. Although the overall recurrence rate (21%, seven of 33 evaluated) was not different from previously published long-term studies, in three of seven cases of recurrence, early recurrences were noted between 2 and 4 months after remission. In patients who did not achieve remission, the most common and effective treatment options were repeat TSS, gamma-knife radiosurgery, and bilateral adrenalectomy. CONCLUSION: The lower remission rate in patients without histological evidence of an adenoma is most likely a result of a decreased rate of adenoma extirpation. The incidence of early recurrence may be a unique feature of this patient population; patients without histological confirmation of tumor resection therefore require close and consistent monitoring postoperatively.
Outcome of non-functioning pituitary adenomas that regrow after primary treatment: a study from two large specialist UK centers
AbstractIntroduction: Despite the significant risk of regrowth of non-functioning pituitary adenomas (NFAs) after primary treatment, systematic data on the probability of further tumour progression and the effectiveness of management approaches are lacking.<br/><br/>Aims: Assess the probability of further regrowth(s), predictive factors and outcomes of management approaches in patients with NFA diagnosed with adenoma regrowth after primary treatment (surgery combined or not with radiotherapy) in two UK referral centers.<br/><br/>Methods: The records of the patients with NFA who during their follow-up had adenoma regrowth were reviewed. The period covered for the primary NFA surgery was between 1/1963 and 12/2011 and the follow-up period ended in 6/2016.<br/><br/>Results: We identified 237 patients (median follow-up after 1st regrowth of 5.9 years (range 0.4–37.7)). The 5-year 2nd regrowth rate was 35.3% (36.2% after surgery; 12.5% after radiotherapy; 12.7% after surgery combined with radiotherapy; 63.4% with monitoring). Of those managed by monitoring, 34.8% eventually were offered intervention. Type of management and sex were risk factors for 2nd NFA regrowth, whereas age at diagnosis of primary NFA and type of adenoma immunostaining were not. Amongst those with 2nd adenoma regrowth, the 5-year 3rd regrowth rate was 26.4% (24.4% after surgery; 0.0% after radiotherapy; 0.0% after surgery combined with radiotherapy; 48.3% with monitoring). Overall, patients with a NFA regrowth had probability of a 3rd regrowth 4.4% at 5 years, and 10.0% at 10 years, and the type of management of the 1st regrowth was the only risk factor. Malignant transformation was diagnosed in two of 237 patients (one gonadotroph and one silent ACTH adenoma).<br/><br/>Conclusions: Patients with regrown NFA after primary treatment continue to carry considerable risk of tumour progression necessitating long-term follow-up. Management approach of the regrowth is the major factor determining this risk; monitoring alone is associated with high progression rates and a substantial number of patients will ultimately require intervention.<br/>
Journal of Neurological Surgery Part B Skull Base · 2023 · 0 citations
Natural History of Long-Term Observed Nonfunctioning Pituitary Adenomas: 434 Consecutive Cases of a Single Institute
AbstractIntroduction: Surgical treatment for nonfunctioning adenoma (NFPA) is indicated when it grows rapidly or worsens visual or endocrine symptoms. However, since standard treatment guidelines for NFPA have not been established, surgical treatment is being performed at various time points in actual clinical practice. It is essential to establish the natural history of NFPA, especially since it is difficult to predict the growth of NFPA. We aimed to establish a natural course of NFPA by following up with 434 patients with NFPA.
Chinese Clinical Oncology · 2024 · 0 citations · open access
AB031. Endoscopic transsphenoidal surgery for functional pituitary adenoma: shifting paradigms towards pseudocapsule-based resection
AbstractBACKGROUND: Functional pituitary adenomas (PAs) manifest as intricate clinical syndromes, and surgery emerges as the principal intervention to mitigate associated morbidity and mortality. The endoscopic transsphenoidal surgery (ETS) approach stands as the preferred method for addressing PAs, with postoperative remission acting as a pivotal prognostic factor. METHODS: This study seeks to evaluate the influence of different surgical techniques and complications of ETS on functional PAs, focusing on both Acromegaly and Cushing's disease (CD). Patient records, including characteristics, perioperative assessments, postoperative complications, and follow-up data, were systematically gathered. Tumor resection methods were categorized into: (I) complete pseudocapsule resection; and (II) complete piecemeal resection. Post-surgery, daily monitoring of serum cortisol levels continued for a consecutive 3-day period until values of 2 µg/dL or less were achieved. Growth hormone levels were reassessed 12 weeks later, targeting a level of <0.14 g/L. A follow-up enhanced magnetic resonance imaging examination was conducted 3 months post-surgery to confirm the absence of residual tumors. RESULTS: The study identified 46 patients (23 with acromegaly and 13 with CD) who underwent endoscopic surgery between 2020 and 2023. Twenty-six patients underwent piecemeal resection (January 2020 to December 2022), while 10 patients underwent complete pseudocapsule removal (January to December 2023). No significant changes in surgical complications were observed between the two techniques. No instances of carotid artery injury, epistaxis, intracranial infection, or loss of olfaction were reported. In the pseudocapsule group, one patient experienced transient vision loss. Notably, 80% of patients in the pseudocapsule group achieved remission as compared to 57.7% in the piecemeal group. CONCLUSIONS: Pseudocapsule-based resection exhibited a remarkable remission rate, a low complication rate, and an absence of recurrence in functional adenoma patients. Despite the limited number of cases and our early experience, further studies are warranted to validate its effectiveness and safety.
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.
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