DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for leptomeningeal metastasis — screening already-approved drugs against its 15-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLeptomeningeal metastasis maps to a 15-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
approvedMethotrexateApproved drug
Structures already discussed alongside leptomeningeal metastasis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
E. COLI THYMIDYLATE SYNTHASE — Methotrexate has a real, experimentally solved structure in complex with this target (PDB 1AXW, 1.7 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 mtxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1AXW · 1.7 Å · ligand Methotrexate (MTX). Experimental structure, not a prediction.
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 Oncology · 2023 · 92 citations · open access
Leptomeningeal Metastasis: A Review of the Pathophysiology, Diagnostic Methodology, and Therapeutic Landscape
AbstractThe present review aimed to establish an understanding of the pathophysiology of leptomeningeal disease as it relates to late-stage development among different cancer types. For our purposes, the focused metastatic malignancies include breast cancer, lung cancer, melanoma, primary central nervous system tumors, and hematologic cancers (lymphoma, leukemia, and multiple myeloma). Of note, our discussion was limited to cancer-specific leptomeningeal metastases secondary to the aforementioned primary cancers. LMD mechanisms secondary to non-cancerous pathologies, such as infection or inflammation of the leptomeningeal layer, were excluded from our scope of review. Furthermore, we intended to characterize general leptomeningeal disease, including the specific anatomical infiltration process/area, CSF dissemination, manifesting clinical symptoms in patients afflicted with the disease, detection mechanisms, imaging modalities, and treatment therapies (both preclinical and clinical). Of these parameters, leptomeningeal disease across different primary cancers shares several features. Pathophysiology regarding the development of CNS involvement within the mentioned cancer subtypes is similar in nature and progression of disease. Consequently, detection of leptomeningeal disease, regardless of cancer type, employs several of the same techniques. Cerebrospinal fluid analysis in combination with varied imaging (CT, MRI, and PET-CT) has been noted in the current literature as the gold standard in the diagnosis of leptomeningeal metastasis. Treatment options for the disease are both varied and currently in development, given the rarity of these cases. Our review details the differences in leptomeningeal disease as they pertain through the lens of several different cancer subtypes in an effort to highlight the current state of targeted therapy, the potential shortcomings in treatment, and the direction of preclinical and clinical treatments in the future. As there is a lack of comprehensive reviews that seek to characterize leptomeningeal metastasis from various solid and hematologic cancers altogether, the authors intended to highlight not only the overlapping mechanisms but also the distinct patterning of disease detection and progression as a means to uniquely treat each metastasis type. The scarcity of LMD cases poses a barrier to more robust evaluations of this pathology. However, as treatments for primary cancers have improved over time, so has the incidence of LMD. The increase in diagnosed cases only represents a small fraction of LMD-afflicted patients. More often than not, LMD is determined upon autopsy. The motivation behind this review stems from the increased capacity to study LMD in spite of scarcity or poor patient prognosis. In vitro analysis of leptomeningeal cancer cells has allowed researchers to approach this disease at the level of cancer subtypes and markers. We ultimately hope to facilitate the clinical translation of LMD research through our discourse.
Current Opinion in Neurology · 2009 · 51 citations
Leptomeningeal metastasis
AbstractPURPOSE OF REVIEW: Leptomeningeal metastasis occurs in approximately 5% of all patients with cancer. This review summarizes recent literature regarding methods of diagnosis and treatment of leptomeningeal metastasis. RECENT FINDINGS: Staging of leptomeningeal metastasis should include contrast-enhanced brain and spine MRI, and though controversial, radionuclide cerebrospinal fluid (CSF) flow study. Treatment of leptomeningeal metastasis often requires involved-field radiotherapy to bulky or symptomatic disease sites as well as intra-CSF and systemic chemotherapy. The use of high-dose systemic therapy may benefit patients with leptomeningeal metastasis and obviate the need for intra-CSF chemotherapy. Intra-CSF drug therapy primarily utilizes one of three chemotherapeutic agents [i.e. methotrexate, cytosine arabinoside (both free and liposomal) and thio-tetraethylenepentamine] administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Novel intra-CSF agents increasingly utilized in the treatment of leptomeningeal metastasis are targeted mAbs such as rituximab and trastuzumab. SUMMARY: Although treatment of leptomeningeal metastasis is palliative with median patient survival of 2-3 months, treatment may afford stabilization and protection from further neurologic deterioration in patients with leptomeningeal metastasis.
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.
