DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for neuroblastoma — screening already-approved drugs against its 40-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNeuroblastoma maps to a 40-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
approvedVincristineApproved drug
Structures already discussed alongside neuroblastoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
bovine ABCC1 — Vincristine has a real, experimentally solved structure in complex with this target (PDB 9LGC, 2.95 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 r1qdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9LGC · 2.95 Å · ligand Vincristine (R1Q). Experimental structure, not a prediction.
What the evidence adds up to
Neuroblastoma is the most common and deadliest tumour of infancy, accounting for 15% of deaths from paediatric cancer, and its incidence has increased over the last decade. The disease spectrum ranges from spontaneous regression without intervention to treatment-resistant metastatic tumours with poor survival. In a US population-based study of 250 patients diagnosed in 2010–2011, 76% were enrolled on an open clinical trial. All low-risk patients received surgery alone. Most intermediate-risk patients (81%) received a chemotherapy regimen containing carboplatin, etoposide, cyclophosphamide and doxorubicin. High-risk patients received multimodal treatment including chemotherapy, surgery, myeloablative chemotherapy with stem cell rescue, radiation, immunotherapy with dinutuximab, and isotretinoin. At a maximum of 60 months of follow-up, 21% of patients had died. Five-year estimated survival was lower for patients with stage 4 disease, unfavourable DNA ploidy, MYCN amplification, or high-risk classification. Despite multimodal therapy, there has been no significant increase in 5-year survival in the last decade, and only one new drug has been approved for neuroblastoma in the last 30 years.
Four of eight human neuroblastoma cell lines formed tumourspheres in neural stem cell media, and all lines contained cells expressing stem cell markers including CD133, ABCG2, and nestin. LA-N-5 spheres showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumourigenicity. A nestin-targeted oncolytic herpes simplex virus replicated within and killed these tumour-initiating cells, preventing their ability to form tumours in athymic nude mice. The cancer stem cell theory suggests that rare tumourigenic cells resistant to conventional therapy are responsible for relapse, and oncolytic viruses that circumvent typical drug-resistance mechanisms may represent an effective therapy for these cells.
Drug repurposing is being explored as a cost-effective strategy for neuroblastoma, using existing drugs with known safety profiles to accelerate treatment development. A 2024 review discusses computational and experimental repurposing methods and rational drug design, highlighting examples of repurposed drugs with promising clinical results. However, the same review notes that a significant proportion of high-risk patients remain incurable. Earlier reviews point to ongoing research into tyrosine kinase inhibition, differentiation, pathway inhibition, and immunotherapy, with several targets showing promising results in vivo and under investigation for potential clinical trials. A more precise biological understanding of neuroblastoma causes and the cell of origin is still needed to develop medicines that specifically target molecules within tumour cells and to understand the mechanisms behind treatment resistance.
What is still missing is a comprehensive understanding of the mechanisms of tumourigenesis, resistance to therapies, and relapse. Identifying biomarkers of response to each specific drug and developing predictive preclinical models of the tumour are needed. The clinical trials that would test repurposed drugs in properly stratified patient populations, particularly for high-risk disease, have not yet been completed or funded at scale.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Molecular Neuroscience · 2019 · 294 citations · open access
AbstractNeuroblastoma is a neural crest derived malignancy of the peripheral nervous system and is the most common and deadliest tumor of infancy. It is characterized by clinical heterogeneity with a disease spectrum ranging from spontaneous regression without any medical intervention to treatment resistant tumors with metastatic spread and poor patient survival. The events that lead to the development of neuroblastoma from the neural crest have not been fully elucidated. Here we discuss factors and processes within the neural crest that when dysregulated have the potential to be initiators or drivers of neuroblastoma development. A more precise biological understanding of neuroblastoma causes and cell of origin is highly warranted. This will give valuable information for the development of medicines that specifically target molecules within neuroblastoma cells and also give hint about the mechanisms behind treatment resistance that is frequently seen in neuroblastoma.
Neuroblastoma Cell Lines Contain Pluripotent Tumor Initiating Cells That Are Susceptible to a Targeted Oncolytic Virus
AbstractBACKGROUND: Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers. METHODOLOGY/PRINCIPAL FINDINGS: Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice. CONCLUSIONS/SIGNIFICANCE: These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.
Pediatric Hematology and Oncology · 2017 · 103 citations
Treatment and survival of childhood neuroblastoma: Evidence from a population-based study in the United States
AbstractBACKGROUND: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors, that are treated per risk profile. We sought to describe treatment patterns and survival using population-based data from throughout the United States. MATERIALS AND METHODS: Using the National Cancer Institute (NCI)'s Patterns of Care data, we analyzed treatment provided to newly diagnosed, histologically confirmed neuroblastoma patients in 2010 and 2011, registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries. Data were re-abstracted from hospital records and treating physicians contacted for verification. Application of the Children's Oncology Group (COG)'s 3-level (low, intermediate and high) neuroblastoma risk classification system for therapeutic decision-making provided insight to community-based treatment patterns. Kaplan-Meier survival analyses, based on 5-years of follow-up, were also performed. RESULTS: 76% of the 250 patients were enrolled on an open/active clinical trial. All low-risk patients received surgery. Most intermediate-risk patients (81%) received a chemotherapy regimen that included carboplatin, etoposide, cyclophosphamide and doxorubicin. High-risk patients received extensive, multimodal treatment consisting of chemotherapy, surgery, myeloablative chemotherapy with stem cell rescue (transplant), radiation, immunotherapy (dinutuximab), and isotretinoin therapy. 21% patients had died at the end of the maximum 60-month follow-up period. The 5-year estimated survival rates were lower for patients diagnosed with stage 4 disease, unfavorable DNA ploidy, MYCN gene amplification or classified as high-risk. CONCLUSION: Most neuroblastoma patients are registered on a risk-based open/active clinical trial. Variation in modality, systemic agents and sequence of treatment reflects the heterogeneity of therapy received by these patients.
Current Opinion in Pediatrics · 2009 · 63 citations
Recent advances in neuroblastoma
AbstractPURPOSE OF REVIEW: Although there have been recent advances with multimodal therapy, treatment of neuroblastoma remains a clinical challenge. Despite the identification of several genetic features, there has not been a significant increase in 5-year survival in the last decade. This review will highlight the current operative strategies along with new research developments aimed at improving survival. RECENT FINDINGS: The goal of surgical intervention in the early stages of neuroblastoma is complete curative resection. In advanced-stage disease, tissue biopsy for staging is the initial goal. In recent years, minimally invasive surgery (MIS) is considered in carefully selected patients. Recent advances in neuroblastoma research have focused on tyrosine kinase inhibition, differentiation, pathway inhibition, and immunotherapy. Several of these targets have shown promising results in vivo and are currently under investigation for potential clinical trials. SUMMARY: New information on the importance of cell signaling and the targeting of specific genes of interest are providing key insights into neuroblastoma. Only through the discovery of novel treatment strategies made available through the advancement of research will neuroblastoma be survivable for patients with advanced-stage disease.
Expert Opinion on Pharmacotherapy · 2021 · 9 citations
Advances in pharmacotherapy for neuroblastoma
AbstractINTRODUCTION: Neuroblastoma is the most prevalent cancer type diagnosed within the first year after birth and accounts for 15% of deaths from pediatric cancer. Despite the improvements in survival rates of patients with neuroblastoma, the incidence of the disease has increased over the last decade. Neuroblastoma tumor cells harbor a vast range of variable and heterogeneous histochemical and genetic alterations which calls for the need to administer individualized and targeted therapies to induce tumor regression in each patient. AREAS COVERED: This paper provides reviews the recent clinical trials which used chemotherapeutic and/or targeted agents as either monotherapies or in combination to improve the response rate in patients with neuroblastoma, and especially high-risk neuroblastoma. It also reviews some of the prominent preclinical studies which can provide the rationale for future clinical trials. EXPERT OPINION: Although some distinguished advances in pharmacotherapy have been made to improve the survival rate and reduce adverse events in patients with neuroblastoma, a more comprehensive understanding of the mechanisms of tumorigenesis, resistance to therapies or relapse, identifying biomarkers of response to each specific drug, and developing predictive preclinical models of the tumor can lead to further breakthroughs in the treatment of neuroblastoma.
Expert Opinion on Drug Discovery · 2024 · 4 citations
Advances in the approaches used to repurpose drugs for neuroblastoma
AbstractINTRODUCTION: Neuroblastoma (NB) remains a challenging pediatric malignancy with limited treatment options, particularly for high-risk cases. Drug repurposing offers a convenient and cost-effective strategy for treating rare diseases like NB. Using existing drugs with known safety profiles accelerates the availability of new treatments, reduces development costs, and mitigates risks, offering hope for improved patient outcomes in challenging conditions. AREAS COVERED: This review provides an overview of the advances in approaches used to repurpose drugs for NB therapy. The authors discuss strategies employed in drug repurposing, including computational and experimental methods, and rational drug design, highlighting key examples of repurposed drugs with promising clinical results. Additionally, the authors examine the challenges and opportunities associated with drug repurposing in NB and discuss future directions and potential areas for further research. EXPERT OPINION: The fact that only one new drug has been approved in the last 30 years for the treatment of neuroblastoma plus a significant proportion of high-risk NB patients that remain uncurable, evidences the need for new fast and cost-effective alternatives. Drug repurposing may accelerate the treatment development process while reducing expenses and risks. This approach can swiftly bring effective NB therapies to market, enhancing survival rates and patient quality of life.
Vincristine sulfate and cyclophosphamide for children with metastatic neuroblastoma
AbstractThirty-eight children with metastatic neuroblastoma were given a combination of vincristine sulfate and cyclophosphamide in addition to standard surgical and radiotherapeutic management. The two agents were given intravenously on alternating weeks for 12 weeks or longer. Results were best in eight infants under 1 year, five of whom continued to survive free of disease for 16 months. The overall response rate in patients of all ages was 32% (nine out of 28), and the mean survival was 12 months. The combination of the two agents was effective.
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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