DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for malignant glioma — screening already-approved drugs against its 25-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMalignant glioma maps to a 25-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 malignant 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
isocitrate dehydrogenase (NADP(+)) 1 (IDH1) — IDH1 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 ictdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6BKX · 1.65 Å · ligand ISOCITRIC ACID (ICT). Experimental structure, not a prediction.
What the evidence adds up to
Surgical resection of malignant glioma improves survival compared with biopsy alone, according to a 2009 review of prospective studies. A randomised surgical study on a technique for identifying residual tumour intraoperatively also supported maximal cytoreduction in patients treated by resection. The proposed mechanism is removal of the therapy-resistant, hypoxic, highly-proliferative tumour core. Surgery may also enhance the efficacy of adjunct and adjuvant therapies.
In glioblastoma, the most aggressive primary brain tumour, median survival remains 12–15 months even with the addition of temozolomide chemotherapy to post-operative radiotherapy. A 2008 review of targeted therapeutics for malignant glioma concluded that experience with these agents had been disappointing. The drugs were generally well tolerated, but activity was limited. The review stated that novel therapeutics with activity against malignant gliomas must be identified.
A 2018 study of surgical samples from glioblastoma patients found that the BAF45d/6A splice isoform was present in 85% of over 200 glioma samples analysed. This isoform contributed to the malignant glioma phenotype by maintaining an undifferentiated cellular state. The splicing was mediated by PTBP1, and BAF45d in turn regulated PTBP1, revealing a reciprocal interplay between RNA splicing regulation and transcription. The authors concluded that understanding this aberrant splicing would uncover new therapeutic targets.
What is still missing is a targeted therapy that shows meaningful activity in clinical trials, rather than the limited activity seen so far. The splicing mechanism described has not yet been translated into a drug that improves survival. No randomised data exist to show that targeting BAF45d or PTBP1 alters patient outcomes. The surgical benefit is established, but the gains remain modest. Funding for trials that test new agents against these molecular targets, and better patient stratification to identify who might benefit, are still lacking.
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 Neurology · 2009 · 93 citations
The importance of surgical resection in malignant glioma
AbstractPURPOSE OF REVIEW: There is still controversy surrounding the role of cytoreductive surgery in the management of malignant gliomas because randomized studies have been missing. Here we review recent data from prospective studies that provide novel arguments in support of surgery. RECENT FINDINGS: Presently available studies not only demonstrate a benefit of surgical resection of malignant gliomas compared with biopsy. Data from a randomized surgical study on a technique for identifying residual tumour intraoperatively also substantiate the beneficial role of maximal cytoreduction in patients treated by resection. Potential mechanisms appear to be linked to the removal of the therapy-resistant, hypoxic, and highly-proliferative tumour core. SUMMARY: Clinical data currently available support the use of surgery for the management of malignant glioma. Surgery improves survival and may enhance the efficacy of adjunct and adjuvant therapies.
Neuro-Oncology · 2018 · 28 citations · open access
The aberrant splicing of BAF45d links splicing regulation and transcription in glioblastoma
AbstractBackground: Glioblastoma, the most aggressive primary brain tumor, is genetically heterogeneous. Alternative splicing (AS) plays a key role in numerous pathologies, including cancer. The objectives of our study were to determine whether aberrant AS could play a role in the malignant phenotype of glioma and to understand the mechanism underlying its aberrant regulation. Methods: We obtained surgical samples from patients with glioblastoma who underwent 5-aminolevulinic fluorescence-guided surgery. Biopsies were taken from the tumor center as well as from adjacent normal-appearing tissue. We used a global splicing array to identify candidate genes aberrantly spliced in these glioblastoma samples. Mechanistic and functional studies were performed to elucidate the role of our top candidate splice variant, BAF45d, in glioblastoma. Results: BAF45d is part of the switch/sucrose nonfermentable complex and plays a key role in the development of the CNS. The BAF45d/6A isoform is present in 85% of over 200 glioma samples that have been analyzed and contributes to the malignant glioma phenotype through the maintenance of an undifferentiated cellular state. We demonstrate that BAF45d splicing is mediated by polypyrimidine tract-binding protein 1 (PTBP1) and that BAF45d regulates PTBP1, uncovering a reciprocal interplay between RNA splicing regulation and transcription. Conclusions: Our data indicate that AS is a mechanism that contributes to the malignant phenotype of glioblastoma. Understanding the consequences of this biological process will uncover new therapeutic targets for this devastating disease.
Expert Opinion on Emerging Drugs · 2008 · 18 citations
Emerging drugs for malignant glioma
AbstractBACKGROUND: Malignant gliomas are amongst the most devastating and intractable of all cancers. The most common malignant glioma, glioblastoma multiforme (GBM), is associated with a median survival in the range of 12-15 months. Survival for patients with GBM has improved with the addition of temozolomide chemotherapy to post-operative radiotherapy. Further advances in the treatment of malignant glioma will hinge on the discovery of novel and likely targeted therapies with activity against these diseases. OBJECTIVE: Review recent published experience using targeted therapeutics for malignant glioma. METHODS: Key studies from a Medline review of targeted therapies for malignant glioma performed between 2000 and the present are summarised in this review. CONCLUSIONS: Experience with targeted therapeutics for malignant glioma has been to date disappointing. These agents are generally well tolerated, but activity is limited. Novel therapeutics with activity against malignant gliomas must be identified to improve prognosis for patients with these diseases.
AbstractMalignant gliomas are the most common type of primary malignant brain tumor, and glioblastoma is the most common malignant glioma. Standard initial therapy for glioblastoma includes aggressive surgical resection followed by a combination of focal radiation and chemotherapy with temozolomide; the role for chemotherapy in initial treatment of other malignant gliomas is less clear. Prognosis is poor, and recurrence of any malignant glioma is almost universal. This chapter provides an overview of malignant gliomas, their treatment, and ongoing research looking for more effective treatments.
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.
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.
