DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Pineocytoma — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePineocytoma maps to a 2-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 pineocytoma 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
bromodomain containing 4 (BRD4) — BRD4 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 oxyethane-2,1-diyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6DNE · 2.958 Å · ligand N,N'-[ethane-1,2-diylbis(oxyethane-2,1-diyl)]bis{2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetamide} (H1V). Experimental structure, not a prediction.
What the evidence adds up to
A systematic review of 166 patients found 1- and 5-year progression-free survival rates of 97% and 89% after resection, versus 90% and 75% after biopsy alone. Gross-total resection gave 1- and 5-year progression-free survival of 100% at both time points, compared with 94% and 84% for subtotal resection plus radiation. There was no significant difference in progression-free survival between subtotal resection alone and subtotal resection with radiation. A separate systematic review of 168 patients reported 1- and 5-year overall survival of 91% and 84% for gross-total resection, versus 88% and 17% for subtotal resection plus radiotherapy. Again, adding radiation to subtotal resection did not significantly improve overall survival compared with subtotal resection alone.
A single-institution series of 14 adults reported that among patients with subtotally resected tumours, progression-free survival was significantly longer for those who received adjuvant stereotactic radiosurgery than for those who did not. No patient who received adjuvant radiosurgery showed progression during follow-up (median 53 months). In a series of 15 patients who all underwent attempted total resection with endoscopic assistance, macroscopic and radiological complete removal was achieved in every case; none received radiotherapy, and all were alive without recurrence at a mean follow-up of 4.28 years. The endoscope detected residual tumour in 40% of cases that was then resected.
Two case reports describe a 45-year-old woman whose tumour disappeared on CT three months after 5000 rads of radiation, and a 6-year-old girl whose tumour disappeared after four cycles of intravenous ACNU. Both were recurrence-free at 1 and 1.5 years respectively. A separate series of six patients treated with 4500–5400 cGy focal radiation reported two local recurrences and deaths, one death from Alzheimer’s disease at 29 years, and three patients alive without evidence of disease at 21, 52, and 84 months. Craniospinal radiation was recommended only if staging showed dissemination.
What is still missing: prospective trials large enough to compare subtotal resection with and without radiosurgery, any randomised evidence for chemotherapy, and a clear biological or molecular stratification that might identify which pineocytomas progress despite complete resection.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of neurosurgery · 2010 · 55 citations
Tumor control after surgery and radiotherapy for pineocytoma
AbstractOBJECT: Pineocytoma is a rare tumor, and the current literature on these tumors is primarily composed of case reports and small case series. Thus, recommendations on appropriate treatment of these tumors are highly varied. Therefore, the authors performed a systematic review of the literature on tumor control after surgery for pineocytoma to determine the relative benefits of aggressive resection and postoperative adjuvant radiotherapy. METHODS: A comprehensive search of the published English-language literature was performed to identify studies citing outcome data of patients undergoing surgery for pineocytoma. Determination of rates of progression-free survival (PFS) was performed using Kaplan-Meier analysis. RESULTS: Sixty-four articles met the criteria of the established search protocol, which combined for a total of 166 patients. Twenty-one percent of these patients had undergone a biopsy procedure, 38% had undergone subtotal resection (STR), 42% had undergone gross-total resection, and 28% were treated with radiation therapy. The 1- and 5-year PFS rates for the resection group versus the biopsy group were 97 and 90% (1 year), and 89 and 75% (5 years), respectively (p < 0.05, log-rank test). The 1- and 5-year PFS rates for the GTR group versus the group undergoing STR combined with radiation therapy were 100 and 94% (1 year), and 100 and 84% (5 years), respectively (p < 0.05, log-rank test). There was no significant difference in PFS for STR only compared with STR in addition to radiation therapy. CONCLUSIONS: Gross-total resection is the ideal treatment for pineocytoma and might represent a cure for these lesions. When gross-total resection is not possible, adjuvant radiation therapy after STR is of questionable benefit for these patients.
Journal of Neuro-Oncology · 2010 · 45 citations · open access
Factors influencing overall survival rates for patients with pineocytoma
AbstractGiven its rarity, appropriate treatment for pineocytoma remains variable. As the literature primarily contains case reports or studies involving a small series of patients, prognostic factors following treatment of pineocytoma remain unclear. We therefore compiled a systematic review of the literature concerning post-treatment outcomes for pineocytoma to better determine factors associated with overall survival among patients with pineocytoma. We performed a comprehensive search of the published English language literature to identify studies containing outcome data for patients undergoing treatment for pineocytoma. Kaplan-Meier analysis was utilized to determine overall survival rates. Our systematic review identified 168 total patients reported in 64 articles. Among these patients, 21% underwent biopsy, 38% underwent subtotal resection, 42% underwent gross total resection, and 29% underwent radiation therapy, either as mono- or adjuvant therapy. The 1 and 5 year overall survival rates for patients receiving gross total resection versus subtotal resection plus radiotherapy were 91 versus 88%, and 84 versus 17%, respectively. When compared to subtotal resection alone, subtotal resection plus radiation therapy did not offer a significant improvement in overall survival. Gross total resection is the most appropriate treatment for pineocytoma. The potential benefit of conventional radiotherapy for the treatment of these lesions is unproven, and little evidence supports its use at present.
Long-term radiosurgical control of subtotally resected adult pineocytomas
AbstractOBJECT: The optimal management of pineocytomas remains controversial. Although the value of complete microsurgical removal is well accepted, gross-total resection is not always feasible. Data regarding the role of postoperative adjuvant stereotactic radiosurgery (SRS) for residual disease is limited and conflicting. Here, the authors review the largest single-institution experience with multimodal pineocytoma management in an effort to quantify the utility of adjuvant radiosurgical treatment of residual disease. METHODS: The medical records and radiographic studies for all patients with histologically confirmed pineocytoma at the Barrow Neurological Institute between 1999 and 2011 were retrospectively reviewed. Clinical and radiographic data, including the volumetric extent of resection, were collected retrospectively, and Kaplan-Meier analysis was used to identify progression-free survival. RESULTS: Fourteen adults with newly diagnosed pineocytomas were surgically treated in the period from 1999 to 2011. The median clinical and radiographic follow-ups were 44 and 53 months, respectively. Twelve patients (86%) underwent microsurgical removal and 2 (14%) underwent endoscopic biopsy. Five patients (36%) had complete resections and 9 (64%) demonstrated residual disease. Three patients (21%) presented with radiographic recurrence at a median interval of 43 months after initial treatment (range 13-83 months). At the time of recurrence, the median preoperative tumor volume was 2.6 cm(3). Adjuvant SRS was used to treat 3 subtotally resected tumors (33%) following initial presentation and 2 (66%) at the time of recurrence. Among patients with subtotally resected tumors, progression-free survival was significantly longer (p < 0.05) for those who did as compared with those who did not undergo adjuvant radiosurgery. To date, no patient who underwent adjuvant radiosurgery has demonstrated radiographic or clinical evidence of disease progression. CONCLUSIONS: Microsurgical removal remains the definitive treatment for pineocytomas, yet residual disease can be effectively controlled using adjuvant SRS.
AbstractSix cases of histologically proven pineocytoma are reported. The diagnosis was established by surgery in five cases and at autopsy in one. All patients received focal radiation therapy (4500 to 5400 cGy). Two patients had local recurrences at 1 and 48 months and subsequently died of tumor. A third patient died of Alzheimer's disease 29 years after the initial presentation. Three patients are alive with no evidence of disease at 21+, 52+, and 84+ months after treatment. Tumor dissemination occurred after a local recurrence in one patient. We found no evidence of recurrence outside the irradiated field unless there was an initial recurrence at the primary tumor site. We recommend postoperative staging for all patients with pineocytoma and focal radiation therapy if local disease alone is found. Craniospinal radiation therapy appears to be justified only if tumor dissemination is documented on staging tests.
The Value of Endoscopy in the Total Resection of Pineocytomas
AbstractBACKGROUND: Pineocytomas are rare pineal region tumors. The mainstay of treatment for pineocytomas is total surgical resection. OBJECTIVE: To address the worthiness of endoscopy to achieve total macroscopic resection and whether or not this portends better progression-free and overall survival. METHODS: A series of 15 patients (11 females, 4 males; mean age, 48 years) with histological diagnosis of pineocytoma were retrospectively reviewed. All patients underwent an attempt at total resection via an interhemispheric/transtentorial/retrosplenial approach. The endoscope was used at various times throughout the case and consistently at the end to evaluate any possible residual tumor. No patient in this series was given radiotherapy after surgery. RESULTS: There was no surgical mortality and all patients are currently alive without recurrence (mean follow-up, 4.28 years). A macroscopic and radiological complete removal was achieved in all cases. There was only one patient with permanent neurological deficit (disconjugate eye movements). Two patients (13%) had transient poor sleep pattern, 5 patients (33%) had transient disconjugate eye movements, and 2 patients (13%) had transient short-term memory disturbance. In 6 cases (40%), the endoscope was able to detect residual tumor located either behind the Vein of Galen or attached to the undersurface of the corpus callosum. Residual tumor was then resected using a 30 degrees endoscope and dedicated angled endoscopic instruments. CONCLUSIONS: This series demonstrates the advantage of endoscopic-assisted surgery in the total removal of pineocytomas. With total removal of these histologically benign tumors patients may enjoy extended progression-free survival without adjuvant radiotherapy.
Neurologia medico-chirurgica · 1989 · 18 citations · open access
Responses of Pineocytoma to Radiation Therapy and Chemotherapy
AbstractPineal parenchymal tumors are so rare that their responses to radiation and/or chemotherapy are not well known. Two cases of pineocytoma, which responded well to radiation therapy and chemotherapy, are reported. A 45-year-old female received radiation therapy in a total dose of 5000 rads to the tumor. Three months after the completion of therapy, computed tomography (CT) showed complete disappearance of the tumor, and she remains well as of 1 year after treatment. The second patient, a 6-year-old girl, underwent four cycles of intravenous infusion of ACNU (25 mg) over 10 months. CT demonstrated complete disappearance of the tumor and, 18 months post-operatively, there was no evidence of tumor recurrence. The results in these two cases indicate that postoperative radiation therapy and/or chemotherapy should be strongly considered for patients with pineal parenchymal tumors.
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.
