DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for germ cell tumor — screening already-approved drugs against its 23-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGerm cell tumor maps to a 23-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
approvedVinblastineApproved drug
Structures already discussed alongside germ cell tumor in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Structure of Calmodulin — Vinblastine has a real, experimentally solved structure in complex with this target (PDB 1XA5, 2.12 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet kardrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1XA5 · 2.12 Å · ligand Vinblastine (KAR). Experimental structure, not a prediction.
What the evidence adds up to
In a phase III trial of 35 patients with unresectable late relapse germ cell tumours (relapse more than two years after cisplatin-based chemotherapy), high dose chemotherapy followed by resection of residual lesions in 15 patients (43%) yielded a 15% projected progression-free survival at a median follow-up of 5.6 years. Only 5 of 35 patients (14%) had no progression. The authors state that management for unresectable late relapse remains controversial, though long-term remission is possible in individuals.
A 2015 case report describes a 19-year-old man with a synchronous bilateral testicular teratoma and a mixed germ cell tumour containing choriocarcinoma and embryonal carcinoma. After six cycles of bleomycin, etoposide and cisplatin produced only a partial response, second-line chemotherapy with vincristine, etoposide, ifosfamide and cisplatin was given, but the disease progressed and the patient died. The report notes that 90% of patients diagnosed with germ cell tumours can be cured, but that delay in diagnosis correlates with advanced stage and poor prognosis.
A 2007 review summarises that attenuations in the rising incidence of testicular germ cell tumours are beginning to be observed in certain European populations, and that late relapses of successfully treated patients are increasingly recognised. The review states that more effective treatments for intermediate-risk, poor-risk and recurrent germ cell tumours need to be developed, and that long-term toxicities of therapies need to be further modified.
A 2002 paper describes a stage IV undifferentiated germ cell tumour treated with a PEP regimen (cisplatin, etoposide, bleomycin) and concludes that this regimen is effective for metastatic disease, but provides no survival or response numbers. A 2014 report from Saint Petersburg notes that lack of awareness among young men and general practitioners often causes late medical aid and diagnostic errors, and that reducing the time to diagnosis may improve survival rates, but gives no quantitative data.
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 Urology · 2010 · 34 citations
High Dose Chemotherapy as Salvage Treatment for Unresectable Late Relapse Germ Cell Tumors
AbstractPURPOSE: We assessed the activity of high dose chemotherapy in patients with unresectable late relapse germ cell tumors. MATERIALS AND METHODS: A total of 35 patients with late relapse were included in a group of 216 treated with high dose chemotherapy as first or subsequent salvage treatment in a prospective, randomized, multicenter phase III trial comparing single vs sequential high dose chemotherapy. Late relapse was defined as unequivocal evidence of relapse more than 2 years after completion of cisplatin based chemotherapy. All patients were considered to have unresectable, progressive, late relapse germ cell tumors. Responders were scheduled for surgical resection of all residual lesions when technically feasible. RESULTS: We identified 4 late relapse groups, including late relapse in 20 of 35 patients (57%) after first line treatment (group 1), in 4 (11%) after first salvage treatment (group 2), in 4 (11%) after initial and after first salvage treatment (group 3), and in 7 (20%) after first line treatment and salvage treatment with rapid progression thereafter who were randomized to a high dose chemotherapy trial (group 4). Median time to late relapse was 4.7 years (range 2.1 to 18.3) in all groups. Resection of all residual lesions could be done in 15 of 35 patients (43%). At a median followup of 5.6 years (range 1.9 to 8.5) 5 of 35 patients (14%) had no progression, resulting in 15% projected progression-free survival. CONCLUSIONS: Management for unresectable late relapse germ cell tumors remains controversial. High dose chemotherapy followed by resection of all residual lesions can result in long-term remission in individuals.
AbstractPURPOSE OF REVIEW: Preclinical and clinical developments in germ cell tumors over the past year are summarized. RECENT FINDINGS: Attenuations in the rising incidence of testicular germ cell tumors are beginning to be observed in certain European populations. Additional data on predisposing factors related to race, estrogenic exposure, cryptorchidism, and infertility are becoming available. Significant work on the genetic and molecular alterations in tissue specimens and cell culture models of germ cell tumors continues. Additional treatment strategies for advanced stages of the disease are being evaluated. Cardiovascular and metabolic consequences of therapies in long-term testicular germ cell tumor survivors are being further clarified. Late relapses of successfully treated patients are also being increasingly recognized. SUMMARY: More effective treatments for intermediate risk, poor risk, and recurrent germ cell tumors need to be developed, while long-term toxicities of therapies need to be further modified. Given these challenges, active research on these fronts continues and remains a priority.
Gynecologic and Obstetric Investigation · 2002 · 4 citations
Dysgerminoma in a Patient with a Tumor of the Neck
AbstractThe evolution of therapy for malignant ovarian germ cell tumors is one of the true success stories in oncology. Treatment outcome has improved greatly thanks to cisplatin-based combination chemotherapy. According to the well-established treatment guidelines for advanced cases, we treated a case of stage IV undifferentiated germ cell tumor in which we were able to preserve the patient's fertility. We concluded that the PEP regimen is an effective treatment for the patient with metastatic germ cell tumor.
Cirugía y Cirujanos · 2015 · 2 citations · open access
Teratoma testicular bilateral sincrónico: reporte de un caso y revisión de la literatura
AbstractEl cáncer testicular de células germinales es la neoplasia más frecuente en hombres de 15 a 35 años de edad; es bilateral en el 2 al 3%, y sincrónico en el 20 al 25% de los casos. Masculino de 19 años de edad, con dolor abdominal y tumor palpable en mesogastrio. En la tomografía se encontró un tumor retroperitoneal, y por laboratorio se detectó elevación de α-fetoproteína, deshidrogenasa láctica y gonadotropina coriónica humana. En el ultrasonido testicular se identifican lesiones bilaterales. Se realizó laparotomía exploradora, identificándose tumor retroperitoneal irresecable, y se tomaron biopsias incisionales compatibles para tumor de células germinales mixto, con áreas de coriocarcinoma y carcinoma embrionario. Se administraron 6 ciclos de quimioterapia con bleomicina, etopósido y cisplatino, obteniéndose una respuesta tumoral parcial. Posteriormente se realizó orquiectomía radical bilateral, con reporte patológico de teratoma bilateral sincrónico. Se inició segunda línea de quimioterapia con vincristina, etopósido, ifosfamida y platino; sin embargo, la enfermedad progresó, presentando diseminación metastásica y provocando el deceso del paciente. Los tumores de células germinales pueden presentarse en sitios primarios extragonadales. Es difícil distinguir un tumor de células germinales primario del retroperitoneo, de una enfermedad metastásica derivada de un tumor gonadal no detectado clínicamente, o que ha involucionado, situación que se describe en el caso clínico presentado. El 90% de los pacientes diagnosticados con tumor de células germinales pueden ser curados; sin embargo, un retraso en el diagnóstico se correlaciona con una etapa clínica más avanzada y un pronóstico desfavorable. Testicular germ-cell carcinoma is the most frequent neoplasm in males aged 15 to 35 years old. It is bilateral in 2% to 3%, and synchronous in 20% to 25% of the cases. The case is presented of a 19 year-old male, with abdominal pain. Physical examination revealed abdominal mass in the umbilical region, and the computed tomography scan showed a retroperitoneal tumour, with α-fetoprotein, lactate dehydrogenase, and human chorionic gonadotropin above limits. Testicular ultrasound showed bilateral lesions. Exploratory laparotomy was performed, identifying an unresectable retroperitoneal tumour. Biopsies were taken, reporting mixed germ cell tumour composed of choriocarcinoma and embryonal carcinoma. Six cycles of chemotherapy were given, based on bleomycin, etoposide and cisplatin, with partial tumour response. Later on, the patient underwent bilateral radical orchiectomy, with pathology reporting a synchronous bilateral testicular teratoma. A second line of chemotherapy was given, based on vincristine, etoposide, ifosfamide and cisplatinum. Nevertheless, the disease progressed, with metastatic dissemination and the patient died. Germ cells tumours can present in primary extra-gonadal locations. It is difficult to distinguish a retroperitoneum primary germ cell tumour from metastatic disease of a clinically undetected gonadal tumour or one that has regressed, like the situation described in the case presented. Ninety percent of patients diagnosed with germ cell tumours can be cured. However, delay in diagnosis correlates with an advanced clinical stage and poor prognosis.
Oncourology (Russian Society of Oncourologists) · 2014 · 1 citations · open access
IMPACT OF DELAYED PREHOSPITAL DIAGNOSIS ON THE RESULTS OF TREATMENT IN PATIENTS WITH GERMINOGENIC TESTICULAR TUMORS IN SAINT PETERSBURG
AbstractOver the past quarter-century germ cell tumors are one of the few cancers for which highly effective treatment is found. However there is a lack of awareness of young men and general practitioners about germ cell tumors which is often cause of late medical aid appealability and potential diagnostic errors. Reducing the time between patient's medical aid appealability and final diagnosis may contribute to the diagnostics of germ cell tumors in the early stages, reducing the amount of treatment and improving survival rates.
The Medical Journal of Australia · 1979 · 1 citations
ADVANCED MALE NON‐SEMINOMATOUS GERM‐CELL TUMOURS
AbstractNineteen men with advanced germ-cell tumours were treated with a combination of vinblastine, bleomycin and cis-diamminedichloroplatinum II (cis-platinum). One patient died nine days after starting chemotherapy. Seventeen patients responded to therapy (14 completely and three partially). Toxicity was very high, and three patients died of septicaemia during therapy. Eight patients remain in complete remission 36 to 80 weeks after starting chemotherapy.
Russian journal of neurosurgery · 2019 · 0 citations · open access
Primary germ cell tumors of the central nervous system
AbstractThe study objective is to describe current views on pathogenesis, molecular biology, diagnosis, treatment of primary germ cell tumors of the central nervous system, as well as treatment prognosis. Materials and methods . The review includes 51 literature sources (4 in Russian, 47 in English). All articles were published in the last 20 years. Results and conclusion. The review reflects both established principles and characteristics of the national protocol of treatment of germ cell tumors, treatment nuances determined by histological type of the tumor. The most effective treatment method for germ cell tumors are radiation and neoadjuvant chemotherapy. For non-germinal germ cell tumors chemotherapy with subsequent complete removal is optimal. Total tumor resection by itself is the ideal treatment of mature teratomas. In the future, molecular and cytogenetic studies will allow to additionally identify subtypes of germ cell tumors of the central nervous system which will become the basis of new directions for therapy, improved treatment results and methods of prognosis.
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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