DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Hepatoblastoma — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHepatoblastoma maps to a 46-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 hepatoblastoma 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
renin (REN) — REN 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 2-bromo-5-fluorophenoxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3K1W · 1.5 Å · ligand 4-{4-[3-(2-bromo-5-fluorophenoxy)propyl]phenyl}-N-(2-chlorobenzyl)-N-cyclopropyl-1,2,5,6-tetrahydropyridine-3-carboxamide (BFX). Experimental structure, not a prediction.
What the evidence adds up to
Hepatoblastoma is the most common malignant liver tumour in childhood. International collaborative efforts have led to uniform use of the PRETEXT staging system to assess upfront resectability. Multimodal therapy consists of chemotherapy and surgical intervention; complete surgical resection is central to successful treatment. Outcomes have improved over the past four decades due to advances in chemotherapeutic agents and surgical approaches including vascular exclusion, ultrasonic dissection, and liver transplantation. Challenges remain in managing high-risk patients and those with recurrent or metastatic disease. A more individualised approach to different types of hepatoblastoma may become the basis of treatment for complex or advanced cases.
The survival rate for patients with metastatic hepatoblastoma increased from 27% to 79% over the thirty years up to 2020, attributed to risk stratification, chemotherapy, and surgical care. Patients with poor prognosis still require more effective therapies. Recent insights into the biology of hepatoblastoma have set the stage for molecular classification and identification of new targets. In vivo models are being used to elucidate mechanisms of disease development and to test new treatment modalities in the pre-clinical phase.
In adults, hepatoblastoma is extremely rare. A review of fifteen cases found a slight female preponderance; patient age ranged from 17 to 82, with a median survival time of 6 months (range two weeks to 38 months). Diagnosis was not identified until tumour biopsy after operation or autopsy. Complete surgical resection is considered the only chance of a better prognosis, and chemotherapy as adopted in children is recommended. The prognosis is poor, and awareness of the condition in the differential diagnosis of liver tumours could be beneficial.
A retrospective study of 27 paediatric patients treated between 1994 and 2009 reported median follow-up and survival rates of 100% for PRETEXT group I (median follow-up 2.3 years), 75% for group II (6.6 years), 92% for group III (5.8 years), and 100% for group IV (7.7 years). Complete excision was achieved in all patients except one who underwent liver transplantation. Four patients died: causes were cytomegalovirus hepatitis, bone marrow suppression during adjuvant chemotherapy, primary nonfunction after transplantation for recurrent tumour, and metachronous rectal cancer. The treatment of relapsing hepatoblastoma has remained troublesome; therapeutic options include re-operation, chemotherapy, radiotherapy, and targeted therapy. What is still missing are effective therapies for high-risk and relapsed disease, prospective trials in adults, and validated molecular targets that can be translated from preclinical models into stratified clinical trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Pediatrics · 2014 · 106 citations
Management of hepatoblastoma
AbstractPURPOSE OF REVIEW: To summarize the current standards and guidelines for the diagnosis and management of hepatoblastoma, a rare pediatric liver tumor. RECENT FINDINGS: Hepatoblastoma is the most common malignant liver tumor in childhood. International collaborative efforts have led to uniform implementation of the pretreatment extent of disease (PRETEXT) staging system as a means to establish consensus classification and assess upfront resectability. Additionally, current histopathological classification, in light of more advanced molecular profiling and immunohistochemical techniques and integration of tumor biomarkers into risk stratification, is reviewed. Multimodal therapy is composed of chemotherapy and surgical intervention. Achievement of complete surgical resection plays a key role in successful treatment for hepatoblastoma. Overall, outcomes have greatly improved over the past four decades because of advances in chemotherapeutic agents and administration protocols as well as innovations of surgical approach, including the use of vascular exclusion, ultrasonic dissection techniques, and liver transplantation. Challenges remain in management of high-risk patients as well as patients with recurrent or metastatic disease. SUMMARY: Eventually, a more individualized approach to treating the different types of the heterogeneous spectrum of hepatoblastoma, in terms of different chemotherapeutic protocols and timing as well as type and extent of surgery, may become the basis of successful treatment in the more complex or advanced types of hepatoblastoma.
Translational Gastroenterology and Hepatology · 2020 · 29 citations · open access
Hepatoblastoma: current knowledge and promises from preclinical studies
AbstractAbstract: The survival rate for patients with metastatic hepatoblastoma (HB) is steadily increased in the last thirty years from 27% to 79%. These achievements result from accurate risk stratification and effective chemotherapy and surgical care. However, patients with poor prognosis require more effective therapies. Recent years have witnessed new insights on the biology of HB, setting the stage for molecular classification and new targets of therapy. We review here the molecular pathology of HB, focusing on the driver genes involved in the process of oncogenesis and the identification of novel targets. We also address the role of in vivo models in elucidating the mechanisms of development of this disease and the pre-clinical phase of new treatment modalities.
Journal of Clinical Medicine Research · 2009 · 28 citations · open access
Hepatoblastoma in Adult: Review of the Literature
AbstractUNLABELLED: This study is to review and retrieve data on adult hepatoblastoma (HB) from English literatures in order to gain a better understanding of this disease. We performed Medline, PubMed (from January 1966 to February 2008), and library searches (National Science and Technology Library, Beijing, China, and Wenzhou Medical College Library, from January 1980 to February 2008) using the key words hepatoblastoma in adult, hepatic tumor, hepatoblastoma and adult. Previously reported HB cases were collected and published reviews were also examined. Fifteen cases that met the search criteria were selected. Review of the cases revealed a slight female preponderance. The patients' age ranged from 17 to 82, with median age of 70 for male and 27 for female. The survival time ranged from two weeks to 38 months, and the median survival time was 6 months. In the articles reviewed, HB presented with non-specific initial symptoms, and the diagnosis was not identified until the tumor biopsy after operation or autopsy. Completely surgical resection is still the major treatment for patients with HB and is considered as the only chance of a better prognosis. Due to the rareness of HB in adults, the choice of treatment should be radical resection if possible, and combined with chemotherapy as adopted in children. HB in the adult is extremely rare and the pre-operative diagnosis is often overlooked. The prognosis is so poor that the awareness of the condition in the differential diagnosis in liver tumors could be beneficial. KEY WORDS: Hepatoblastoma; Adult; Diagnosis; Therapy.
Journal of the Korean Surgical Society · 2011 · 19 citations · open access
Hepatoblastoma: 15-year experience and role of surgical treatment
AbstractPURPOSE: Hepatoblastoma is the most common malignant liver tumor in children. The aim of this study was to review our results of hepatoblastoma treatment and to determine the role of surgical treatment in hepatoblastoma. METHODS: This is a retrospective clinical study. The medical records of patients with hepatoblastoma, treated between October 1994 and October 2009, were reviewed. The patients were classified according to the pretreatment extent of disease (PRETEXT) grouping system. The main outcome variable was survival. Secondary outcome variables were complete, partial and no response to chemotherapy and surgery, when indicated. RESULTS: Twenty-seven patients were treated during the observation period. Eighteen were males. Five were PRETEXT group I, 8 group II, 13 group III and 1 group IV. Complete excision was achieved in all patients except in one case that underwent liver transplantation (group IV). Median follow-up and survival rate were 2.3 years and 100%, 6.6 years and 75%, 5.8 years and 92%, 7.7 years and 100%, for groups I to IV, respectively. Twenty patients are currently considered to be in complete response status and three patients are receiving postoperative chemotherapy. Four patients died; the causes of death were cytomegalovirus hepatitis, bone marrow suppression during adjuvant chemotherapy, primarynonfunction after the transplantation for recurrent tumor and metachronous rectal cancer, respectively. CONCLUSION: Favorable long-term outcome could be expected for hepatoblastoma with complete tumor excision and adjuvant chemotherapy.
AbstractThe treatment of relapsing hepatoblastoma has remained troublesome.The characteristics of relapsing hepatoblastoma are summarized, including recurrence sites, recurrence rates and risk factors.Then therapeutic options are re-operation, chemotherapy, radiotherapy and targeted therapy, etc.Both clinical applications and basic sciences are discussed.Furthermore, the efficacies of various treatments are compared.
Key words:
Hepatoblastoma; Relapse; Treatment
Sage Journals Data · 2023 · 0 citations · open access
sj-xlsx-4-pdp-10.1177_10935266231204788 – Supplemental material for Molecular Profiling of a Hepatocellular Neoplasm Not Otherwise Specified (HCN-NOS) Demonstrates Distinct Molecular Features in Hepatoblastoma and HCC-Like Components
AbstractSupplemental material, sj-xlsx-4-pdp-10.1177_10935266231204788 for Molecular Profiling of a Hepatocellular Neoplasm Not Otherwise Specified (HCN-NOS) Demonstrates Distinct Molecular Features in Hepatoblastoma and HCC-Like Components by Yan Chen Wongworawat, Stephen F. Sarabia, Martin Urbicain, Paola Francalanci, Pavel Sumazin, Rita Alaggio and Dolores H. López-Terrada in Pediatric and Developmental Pathology
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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