DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for brain glioma — screening already-approved drugs against its 41-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBrain glioma maps to a 41-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 brain glioma 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
protein tyrosine phosphatase receptor type D (PTPRD) — PTPRD 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 flcdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2YD6 · 1.35 Å · ligand CITRATE ANION (FLC). Experimental structure, not a prediction.
What the evidence adds up to
Gliomas, particularly glioblastoma, remain highly lethal. A 2001 review notes that even intensive combinations of radio- and chemotherapy are not curative and yield only a modest impact on survival, with long-term survivors under 10%. A 2021 integrated analysis of glioblastoma states a median survival of only 15-23 months. The molecular basis is increasingly understood: a 2003 review describes stepwise accumulation of deleterious genetic alterations in glial-lineage tumors, while a 2021 analysis identified 3088 differentially expressed genes and 43 mRNA-miRNA interactions during disease progression, including BOC-SMO and BOC-RAS promoting malignant progression. A 2021 review of glioma cell biology emphasises tumour heterogeneity and a neuronal-glioma network as mechanisms underlying treatment resistance.
Preclinical combination therapy in rodent orthotopic brain tumour xenografts, reported in 2015, combined intraperitoneal rapamycin with convection-enhanced delivery of nanoliposomal CPT-11, a topoisomerase I inhibitor. The authors report a 6-fold increase in survival in xenotransplanted animals without a rise in toxicity, and propose this as a powerful new combination therapy. This is a single animal study, and no human data are presented.
For low-grade gliomas, management remains controversial. A 2002 review notes that local recurrence and conversion to malignant glioma are the expected outcome within 4-8 years from diagnosis, yet the correct timing and dosage of radiotherapy are still debated, as are the indications for cytotoxic drugs. A 2005 review agrees that the role and timing of chemotherapy is highly controversial, with treatment generally recommended only in symptomatic cases or radiologic progression. No randomised trial data are cited in these abstracts to settle these questions.
What is still missing is any clinical validation of the rapamycin/CPT-11 combination in humans, and any randomised trial evidence for chemotherapy timing in low-grade gliomas. The molecular targets identified in the 2021 analyses remain unvalidated therapeutically. Patient stratification by genetic subtype is proposed but not yet operational, and funding for prospective trials in a disease with a median survival under two years for glioblastoma remains scarce.
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 Oncology · 2003 · 111 citations
Recent advances in the molecular genetics of primary gliomas
AbstractPrimary brain tumors, particularly glioblastomas, remain a challenge for oncology. Uncontrolled cellular proliferation, lack of apoptosis, invasion, and angiogenesis are among the biologic processes that render these tumors both aggressive and difficult to treat. An understanding of the genetics and molecular events regulating these aggressive tumors is beginning to emerge, partly because of recent knowledge in genomics, gene expression analysis, and mouse tumor models. As a result, it is now generally accepted that brain tumors, particularly those arising from cells of glial lineage, result from stepwise accumulation of deleterious genetic alterations. Several genetic abnormalities have been described, and current research is aimed at elucidating their causal association with brain tumor formation and progression. The purpose of this review is to summarize some of the most important recently published findings on the molecular genetics of primary gliomas.
AbstractGliomas are the most common intracranial malignant tumors in humans, and high-grade gliomas in particular pose a unique challenge due to their propensity for proliferation and tissue invasion. Our understanding of glioma oncogenesis, proliferation, and invasion has been greatly advanced in the past 10 years as researchers have gained a better understanding of the molecular biology of these tumors. This article highlights glioma histopathology, as well as cytogenetic and molecular alterations associated with the pathogenesis of human gliomas. It is hoped that better understanding of the molecular pathogenesis of gliomas will improve tumor classification as well as lead to novel targets for therapy and prognostic markers.
Combination Therapy of Intraperitoneal Rapamycin and Convection- Enhanced Delivery of Nanoliposomal CPT-11 in Rodent Orthotopic Brain Tumor Xenografts
AbstractBACKGROUND: Glioblastoma multiforme (GBM) is the most malignant histological type of glioma. It exhibits an extremely aggressive action including invasion of large zones of brain parenchyma. Even after the application of surgery, radio and chemotherapy, the effect and survival for patients with GBM continue to be very poor. The PI3K/AKT/mTOR is a key pathway in the regulation of the proliferation of cancer cells. This is the reason to consider the mTOR inhibitors such as rapamycin analogs as an encouraging therapy for malignant glioma, but current investigations suggest that single inhibition of mTOR may be insufficient. For this reason, there is a need for the use of more than one agent rationally combined. METHODS: In this study, we have evaluated the therapeutic potential of the combination of two different drugs: intraperitoneal rapamycin and convection enhanced delivery of nanoliposomes containing the topoisomerase I inhibitor CPT-11. The effect was analyzed by flow cytometry, cell growth, immunocytochemistry and immunohistochemistry, and rodent orthotopic xenograft survival analysis. RESULTS: The combination presented remarkable efficacy in a survival study. We present an increase in survival of 6-fold in xenotransplanted animals without rise in toxicity. CONCLUSION: In summary, we propose a very powerful new combination therapy for glioma.
Expert Review of Anticancer Therapy · 2001 · 10 citations
Changing boundaries in the treatment of malignant gliomas
AbstractMalignant gliomas are still among the most lethal and difficult tumors to treat; even the most intensive combinations of radio- and chemotherapy are not curative and yield only a modest impact on survival for most of these patients, as long-term survivors are less than 10%. There is a major need for new chemotherapeutic drugs and alternative therapeutic modalities. This review aims to define the best standard treatment in the common clinical practice and also summarizes the most promising lines of investigational research in the field of neuro-oncology, which will probably offer new and long-awaited valid therapy options for brain tumor patients.
International Journal of General Medicine · 2021 · 6 citations · open access
Integrated Analysis of Mutations, miRNA and mRNA Expression in Glioblastoma
AbstractBACKGROUND: Glioblastoma multiforme (GBM) is a common, malignant brain tumor in adults, with a median survival of only 15-23 months. Organisms respond to disease stress through sophisticated mechanisms at the physiological, transcriptional and metabolic levels. However, the molecular regulatory networks responsible for occurrence, progression and recurrence of glioma have yet to be elucidated. METHODS: In this study, we sought to determine the cause of gliomas by developing an RNA-seq technique that analyzes mRNA and small RNA (sRNA) with the aim of discovering potential methods for precisely blocking key signaling pathways in occurrence, progression, and recurrence. The explication of mechanisms leading to GBM formation has become a feasible and promising new therapeutic method. RESULTS: GBM-associated genes were identified based on their expression during the disease stress response. Analysis of the inverse correlations between microRNAs (miRNAs) and target mRNAs revealed 43 mRNA-miRNA interactions during disease progression. BOC-SMO and BOC-RAS were found to promote the malignant progression of glioma. A total of 3088 differentially expressed genes were identified as involved in several biological processes, such as amino acid metabolism, protein transport associated with immune response, cell proliferation, and cell apoptosis. Fifteen miRNAs were also identified as being differentially expressed in GBM and control groups. CONCLUSION: The results of this study provide an important foundation for understanding the pathogenesis of glioma and discovering new therapeutic targets.
AbstractIn this review, I summarized the biology of gliomas. Through past clinical and basic studies, I reviewed the evidence of the cell of origin of gliomas and the presence of brain tumor-initiating cells in gliomas, which are driven by multiple genomic alterations. In addition, the complicated tumor heterogeneity and neuronal-glioma network were studied. These mechanisms may underlie the treatment resistance and poor prognosis and support the identification of novel therapeutic targets for gliomas.
Expert Review of Anticancer Therapy · 2002 · 4 citations
Controversies in the therapy of low-grade glioma: when and how to treat
AbstractTreatment of low-grade gliomas is one of the most challenging management dilemmas in neuro-oncology. Young age of onset and low rate of growth theoretically favor minimally invasive treatments. Yet, local recurrence and conversion to malignant glioma are the expected outcome within 4-8 years from diagnosis and impose the use of additional therapies, such as radiotherapy and chemotherapy. Due to low incidence and paucity of randomized trials, the correct timing and dosage of radiotherapy are still controversial, as well as the indications and possible benefits of the administration of cytotoxic drugs. Current concepts and future perspectives in the treatment of low-grade gliomas drawn from recent scientific literature are here summarized and discussed.
Expert Review of Neurotherapeutics · 2005 · 4 citations
Chemotherapy for low-grade gliomas
AbstractLow-grade gliomas pose a difficult problem for the neuro-oncologist. More needs to be known about their natural history. In addition, the role and timing of radiotherapy and chemotherapy in the management of low-grade tumors is highly controversial. Most agree that physicians should recommend treatment in symptomatic cases or in instances of radiologic tumor progression. This review discusses some of the recent advances with respect to chemotherapy for low-grade gliomas, with a special emphasis on low-grade astrocytomas and oligodendrogliomas.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, 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.
