DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for germinoma — 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 moduleGerminoma 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 germinoma 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
patched 1 (PTCH1) — PTCH1 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 plmdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6E1H · 3.5 Å · ligand PALMITIC ACID (PLM). Experimental structure, not a prediction.
What the evidence adds up to
In a retrospective UK/German cohort of 58 patients with relapsed intracranial germ cell tumours treated under the SIOP-CNS-GCT-96 protocol, 11 had an initial diagnosis of germinoma. Five-year overall survival for these 11 patients was 55%. Four of six patients whose relapse was still germinoma and two of five whose relapse was non-germinomatous germ cell tumour (NGGCT) were salvaged. Salvage included either standard-dose chemotherapy with re-irradiation or high-dose chemotherapy with autologous stem-cell rescue, with or without re-irradiation. By contrast, among 32 relapsed malignant NGGCT patients treated with curative intent, five-year overall survival was 9% (95% CI 2–26%). No patient receiving standard-dose chemotherapy survived to five years; five-year survival was 14% (3–36%) for those intended for high-dose chemotherapy. The three relapsed NGGCT survivors all had raised HCG markers alone, and two received additional irradiation.
A separate review of pineal germ cell tumours states that germinoma patients treated with radiotherapy alone had a five-year survival above 90%. It adds that adding chemotherapy allowed dose reduction and smaller irradiated fields without loss of curability, but notes that optimal management remains controversial. A single-case report describes a 26-year-old man with a pineal germ cell tumour who underwent radical surgery, relapsed, then received craniospinal radiation and three cycles of cisplatin and etoposide, and was in clinical remission 30 months after treatment.
A study of 52 extremely long-term germinoma survivors treated with radiotherapy between 1968 and 1995 (median dose 48.2 Gy, median follow-up 226 months) reported 10-, 20-, and 30-year actuarial survival rates of 83.6%, 77.5%, and 64.2%. Six patients had tumour recurrence, six developed second tumours, and 12 died, mainly from complications of the primary tumour, its treatment, or recurrence rather than tumour progression. Quality of life was diminished: of 32 patients assessed, 14 had not graduated high school, 21 had no occupation, and 7 of 11 formerly employed patients had left their jobs. Only 6 of 44 patients were married.
A molecular study of 13 germinomas found strong KIT expression in 100% of cases and c-kit gene mutations in 3 tumours (23%). The mutations were missense changes in exons 2, 11, 13, and 17, including novel mutations E73K, T96M, and A636V in one tumour. The presence or type of mutation did not correlate with prognosis. A meta-analysis of 49 biopsied germinoma patients examined beta-HCG thresholds used for diagnosis. Relapse occurred across all three cohorts defined by beta-HCG level (50–100, 100–200, and >200 IU/L), but the groups were small and treatment regimens varied, so no firm conclusions about optimal cut-off could be drawn. What is still missing are prospective trials large enough to stratify patients by beta-HCG level, standardise salvage regimens for relapsed germinoma, and systematically measure long-term quality of life and endocrine outcomes after modern reduced-dose radiotherapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Cancer · 2017 · 54 citations · open access
Treatment and outcomes of UK and German patients with relapsed intracranial germ cell tumors following uniform first-line therapy
AbstractWe aimed to retrospectively assess treatments/outcomes, including the value of high-dose-chemotherapy and autologous-stem-cell-rescue (HDC + AuSCR) and re-irradiation, in a large, European patient-cohort with relapsed intracranial germ-cell-tumors (GCTs) receiving uniform first-line therapy, including radiotherapy as standard-of-care. Fifty-eight UK/German patients (48 male/10 female) with relapsed intracranial-GCTs [13 germinoma/45 non-germinomatous GCT (NGGCT)] treated 1996-2010 as per the SIOP-CNS-GCT-96 protocol were evaluated. For germinoma, six patients relapsed with germinoma and five with NGGCT (one palliative, one teratoma patient excluded). Five-year overall-survival (OS) for the whole-group (n = 11) was 55%. Four of six germinoma relapses and two of five relapsing with NGGCT were salvaged; patients were salvaged with either standard-dose-chemotherapy (SDC) and re-irradiation or HDC + AuSCR with/without re-irradiation. Of 45 relapsed NGGCT patients, 13 were excluded (three non-protocol adherence, five teratoma, five palliation). Five-year OS for the remaining 32 relapsed malignant NGGCT patients treated with curative intent was 9% (95%CI: 2-26%). By treatment received, 5-year OS for the 10 patients receiving SDC and 22 patients treated with intention for HDC + AuSCR was 0% (0-0%) and 14% (3-36%), respectively. The three relapsed NGGCT survivors had raised HCG markers alone; two received additional irradiation. Patients with relapsed germinoma had better 5-year OS than those with relapsed NGGCT (55 vs. 9%; p = 0.007). Patients with relapsed germinoma were salvaged both with SDC and re-irradiation or HDC + AuSCR with/without re-irradiation; both represent valid treatment options. Outcomes for malignant relapse following initial diagnosis of NGGCT were exceptionally poor; the few survivors received thiotepa-based HDC + AuSCR, which is a treatment option at first malignant relapse for such patients, with further surgery/irradiation where feasible.
Journal of Neurosurgery Pediatrics · 2006 · 41 citations
c-<i>kit</i>gene mutation: common and widely distributed in intracranial germinomas
AbstractOBJECT: Of the intracranial germ cell tumors (IGCTs), 10% of germinomas and most nongerminomatous tumors remain refractory to multimodality therapy. The authors investigated the mutation of c-kit and the expression of its product KIT in IGCTs to identify tumors susceptible to imatinib mesylate, a synthetic agent targeting KIT. METHODS: The authors investigated 26 IGCTs, including 13 germinomas, five mixed germ cell tumors (MGCTs), four immature teratomas (ITs), and two each of yolk sac tumors and choriocarcinomas. These tumors were examined for the expression of KIT and CD34 by immunohistochemical analysis, and for mutations in exons 2, 8 to 11, 13, and 17 of c-kit. Strong KIT expression was found in the cell membrane of germinomas (100%) and germinomatous cells of MGCTs (80%), as well as in the cytoplasm of epithelial and smooth-muscle cells of ITs. The membranous expression of CD34 was found in the nongerminomatous tumor cells and the chondrocytes of MGCTs (60%), ITs (100%), and a choriocarcinoma (50%), but not in germinomas and germinomatous cells. A total of five missense mutations distributed in exons 2, 11, 13, and 17 of c-kit were detected in three (23%) of the 13 germinomas. The novel mutations E73K, T96M (both in exon 2), and A636V (in exon 13) were detected in a single tumor. The presence or type of c-kit mutation was not correlated with patient prognosis. CONCLUSIONS: Immunohistochemical analysis of KIT expression is useful for the diagnosis of germinoma. This study may help in clarifying the pathogenesis of IGCTs and in identifying tumors susceptible to drugs targeting KIT.
Feasibility of dasatinib in children and adolescents with new or recurrent central nervous system germinoma
AbstractGerminomas and embryonal carcinomas are central nervous system (CNS) germ cell tumors (GCT) that may overexpress the proto-oncogene c-KIT, a receptor tyrosine kinase, of which dasatinib is a potent inhibitor. This retrospective review presents the feasibility and tolerability of dasatinib administration in select patients with CNS germinoma. Between November 2008 and April 2010, six patients with newly diagnosed (n = 3) or recurrent (n = 3) CNS GCT were treated in an effort to avoid irradiation and/or delay recurrence. The daily doses administered were 100-170 mg/m(2) with mostly grade 1-2 toxicities. Dasatinib may play a role in future treatment strategies for CNS GCT.
Progress in neurological surgery · 2009 · 21 citations
Quality of Life of Extremely Long-Time Germinoma Survivors Mainly Treated with Radiotherapy
AbstractPURPOSE: To assess the quality of life (QOL) of extremely long-time survivors with germinoma mainly treated with radiotherapy. PATIENTS AND METHODS: We enrolled 52 of 68 patients who received radiotherapy between 1968 and 1995 at our hospital. They were 41 males and 11 females; the tumor location was pineal in 20, neurohypophyseal in 15, pineal and neurohypophyseal in 11 patients; in 6 it was located in another region. All underwent radiotherapy; the median dose was 48.2 (range 40.0-60.2) Gy. The median follow-up period was 226 (range 0-448) months. The clinical outcome and QOL were evaluated retrospectively. RESULTS: In 6 patients, the tumor recurred; 6 other patients developed second tumors while in complete remission from the first tumor. The main cause of 12 deaths was complications due to primary tumor invasion, the initial treatment, or tumor recurrence rather than tumor progression. The 10-, 20-, and 30-year actuarial survival rate was 83.6, 77.5, and 64.2%, respectively. Of 44 patients, 6 were married and 3 males with solitary pineal tumors were fathers. Among 32 patients, 14 had, or had not, graduated from high school; the other 18 went on to higher education. Twenty-one patients had no occupation; 7 of 11 formerly employed patients had left their jobs. CONCLUSION: Radiotherapy delivered between 1968 and 1995 to patients with germinoma yielded satisfactory outcomes but a decline in the QOL.
Klinicka onkologie · 2013 · 8 citations · open access
Pineal Germ Cell Tumors: Review
AbstractBACKGROUND: Primary intracranial germ cell tumors represent a rare category of neoplasms, which occur in children and young adults. The WHO classification divides intracranial tumors into germinomas and non-germinomas. The most frequent locality of these tumors is pineal and suprasellar region. Clinical signs and symptoms depend on the localization of the tumour - they most commonly include signs of increased intracranial pressure, Parinauds syndrome, bitemporal hemianopsy and signs of endocrine deficiency. Gadolinium enhanced MRI scan of the brain is the imagining examination of choice in the diagnostic strategy of intracranial germ cell tumors. However, the imagining studies do not provide sufficient information about histological type; therefore, biopsy is necessary. The exception represents cases with characteristically increased levels of tumor markers (AFP and β-HCG) measured in the serum and cere-brospinal fluid. CASE: A pineal germ cell tumor was observed in a 26-year-old male with presentation of an eye-sight disorder with focusing difficulty and photophobia, accompanied by intensive fatigue and sleepiness, nausea with occasional vomiting, intermittent headaches and Parinauds syndrome. MRI examination of the brain showed tumor expansion in the pineal region and in the right part of the mesencephalon. Radical extirpation of the tumor in the pineal region was performed. The follow-up MRI scan of the brain revealed relapse of the disease. The patient underwent craniospinal radiation therapy with subsequent postoperative chemotherapy (regimen cisplatin and etoposide), three cycles in total. Currently, the patient is 30 months after finishing of oncological treatment in clinical remission of the disease. CONCLUSION: The treatment and prognosis of this neoplasm differ between particular categories. Germinomas have better survival rates than non-germinomas. A 5-year survival rate of germinoma patients after application of radiotherapy alone was > 90% of cases. The addition of chemotherapy lead to a decrease of the dose and minimalization of the irradiated area, with achievement of fewer side effects without a decrease of the curability. Non-germinomas are less radiosensitive than germinomas, but after the application of the adjuvant chemotherapy, survival benefit was achieved. However, the optimal management of these tumors remains controversial.
Primary Mediastinal Seminoma and the <sup>67</sup> Gallium Total Body Scan: a Case Report
AbstractWe describe a case in which radionuclide scanning was used for staging and assessing treatment of a germinal neoplasm. Primary mediastinal seminoma is an ectopic manifestation of the not infrequent germinoma. Controversy surrounds the histogenesis of this tumor. Management may include surgery, radiation therapy, chemotherapy or any combination of these. Because of the rather marked radiosensitivity of the tumor the prognosis generally is favorable. The radio-gallium scan was helpful in guiding and following treatment.
GCT-17. EXPLORING NEW THRESHOLDS FOR BETA-HCG IN CENTRAL NERVOUS SYSTEM GERMINOMA
AbstractAbstract BACKGROUND Human chorionic gonadotropin (beta-HCG) levels in serum and cerebrospinal fluid (CSF) are critical in the management of patients with germinoma. The threshold for beta-HCG diagnosis is a topic of debate and differs in Europe, ≤50 IU/L, North America ≤100 IU/L, and ≤200 IU/L in Brazil/Japan. METHODS We conducted a meta-analysis of English-language publications (1990-2023) to assess how beta-HCG cut-off levels impact treatment outcomes. Standard descriptive statistics summarized all data. RESULTS Forty-nine patients with biopsied germinoma were identified. Eighteen had beta-HCG level of 50-100 IU/L (cohort 1), 21 had 100-200 IU/L (cohort 2), and 10 had &gt;200 IU/L (cohort 3). In cohort 1, treatment with chemotherapy plus radiotherapy was administered to 9 patients. Eight of them received radiotherapy like germinoma treatment (≤30Gy), primarily employing whole ventricle irradiation (WVI). Nine patients received radiotherapy alone with total dose 30-59.6Gy. Fifteen patients in cohort 2 received chemotherapy plus radiotherapy. Eight of them received radiotherapy ≤30Gy for different fields [WVI – 4, whole brain (WB) – 3, cerebrospinal irradiation (CSI) – 1). In 7 patients the dose of radiotherapy exceeded 30Gy (local radiotherapy – 4, CSI – 3). Radiotherapy alone was used in 5 patients, chemotherapy alone – 1 patient. In cohort 3, radiotherapy only was primarily used. Six patients received CSI (50-54Gy), one – CSI+WB+local radiotherapy (12.8Gy+27.2Gy+50.6Gy). One patient received combined treatment and 2 patients received chemotherapy alone. Relapses occurred in each cohort. In cohort 1 – 2 metastatic relapses (1 after WVI 24Gy, 1 after radiotherapy &gt;30Gy). Three children from cohort 2, who received chemotherapy plus radiotherapy were diagnosed with relapse (1 after WB 23.4Gy, 2 after radiotherapy &gt;30Gy). In cohort 3 two metastatic relapses were diagnosed – only after chemotherapy. CONCLUSIONS Relapse rates across all beta-HCG level are similar. However, study groups are small and treatment regimens vary, warranting further investigation.
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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