DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for meningioma — screening already-approved drugs against its 48-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMeningioma maps to a 48-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
approvedSunitinibApproved drug
Structures already discussed alongside meningioma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 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 b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
A 2004 review noted that progress in molecular genetics had identified several genes mutated or inactivated in meningiomas, along with chromosomal regions commonly deleted or amplified, suggesting additional tumour suppressor genes or proto-oncogenes. The revised 2000 WHO classification made grading criteria more precise and objective, aiming to improve consistency in predicting recurrence and aggressive behaviour. The review also covered angiogenesis, oedema formation, and the role of hormone receptors.
A 2012 review of articles published from December 2010 to April 2012 reported that large population-based case-control studies had identified new aetiological factors such as smoking and allergy, and new genes involved in meningioma susceptibility. Aggressive surgery remained the treatment of choice, even in the elderly, and postoperative radiotherapy was debated and limited to Grade II residual cases and Grade III tumours. The review stated that there were currently no effective therapies for meningiomas, although preclinical studies had pinpointed candidate drugs such as trabectedin and histone deacetylase inhibitors. Several clinical trials were under way, mostly on heavily pretreated patients, testing platelet-derived growth factor receptor-targeted therapies and antiangiogenic drugs.
A 2015 review reiterated that few medical options were available for progressive or recurrent and atypical or anaplastic meningiomas. It noted that combination therapies affecting multiple molecular targets were opening up and presented significant promise as adjuvant options. However, the review also stated there was an evident need for new molecular studies to better understand meningioma biology and identify more specific therapeutic targets.
What remains missing are effective systemic therapies validated in prospective trials, robust preclinical models that reliably predict human responses, and patient stratification based on molecular subtypes. Funding for adequately powered trials and for the basic biology needed to identify druggable targets is still insufficient.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Neuropathology & Experimental Neurology · 2004 · 228 citations · open access
Meningioma Pathology, Genetics, and Biology
AbstractOver the past 5 to 10 years, important advances were made in the understanding of meningioma biology. Progress in molecular genetics probably represents the most important accomplishment in the comprehensive knowledge of meningioma pathogenesis. Several genes could be identified as targets for mutation or inactivation. Additional chromosomal regions were found to be commonly deleted or amplified, suggesting the presence of further tumor suppressor genes or proto-oncogenes, respectively, in these regions. Histopathologically, the most important innovation is represented by the revised WHO classification in the year 2000. Meningioma grading criteria in the new classification scheme are more precise and objective, and should thus improve consistency in predicting tumor recurrence and aggressive behavior. This review focuses mainly on the advances in molecular biology that were achieved in recent years. It summarizes the most important aspects of meningioma classification as the basis to place biological observations into a correlative context, and, further, includes mechanisms of angiogenesis and edema formation as well as the role of hormone receptors in meningiomas.
AbstractBACKGROUND: Somatostatin receptors, especially the sst2A subtype, are present on most meningiomas. The addition of somatostatin inhibits meningioma growth in vitro in some studies. There have been anecdotal reports of octreotide inhibiting growth in meningiomas. OBJECTIVES: A prospective pilot trial of sustained-release somatostatin (Sandostatin LAR) in 16 patients with recurrent meningiomas was conducted with a primary study objective of progression-free survival at 6 months. METHODS: Sixteen patients (11 women, 5 men; median age 58) with recurrent meningioma were treated prospectively with long-acting somatostatin. Patients had progressed radiographically after prior therapy with surgery (14/16; complete resection in 5; subtotal in 7; biopsy only in 2), radiotherapy (13/16), and chemotherapy (12/16). All patients had confirmation of the presence of somatostatin receptors in their tumor using (111)In-octreotide, a long-acting somatostatin agonist, SPECT scanning. RESULTS: Patients received 2 to 15 cycles (median 4.5) of somatostatin with minimal toxicity. Five [corrected] partial responses, five stable disease, and six [corrected] progressive disease patterns were seen. Duration of response ranged from 2 to 20+ months (median 5.0 months). Median survival was 7.5 months (range 3 to 20+). The overall progression-free survival was 44% (seven patients) at 6 months. CONCLUSIONS: In this small trial of patients with recurrent meningiomas shown to overexpress somatostatin receptors by octreotide scintigraphy, long-acting somatostatin (Sandostatin LAR) was administered on a monthly schedule. Thirty-one percent of patients demonstrated a partial radiographic response and 44% achieved progression-free survival at 6 months. Toxicity was minimal, suggesting somatostatin analogues may offer a novel, relatively nontoxic alternative treatment for recurrent meningiomas.
AbstractPURPOSE OF REVIEW: In view of growing interest and need for nonsurgical therapies of meningiomas, we reviewed relevant articles published in the period from December 2010 to April 2012. RECENT FINDINGS: Large population-based, case-control studies have resulted in identification of new etiology factors, such as smoking or allergy, as well as new genes shown to play a role in meningioma susceptibility. Although aggressive surgery is still the treatment of choice for meningioma patients, even in the elderly population, postoperative radiotherapy remains debated and limited to Grade II residual cases as well as Grade III tumors. Although preclinical studies have pinpointed new candidate drugs to stop meningioma growth, such as trabectedin and histone deacetylase inhibitors, there are currently no effective therapies for meningiomas. Several clinical trials are under way, mostly on heavily pretreated patients, to determine the efficacy of some of the most promising candidate drugs, platelet-derived growth factor receptor-targeted therapies, and antiangiogenetic drugs being on the top list. Robust genetically engineered mouse models should be used as 'filters' to select agents for human clinical trials. SUMMARY: Surgical approach combined with radiotherapy in selected cases remains the most appropriate for meningioma patients. New therapies are under investigation and should modify treatment paradigms in the future.
Innovative Therapeutic Strategies in the Treatment of Meningioma
AbstractFew medical options are available for progressive/recurrent and atypical/anaplastic meningiomas. New developments in chemotherapeutic options for meningiomas have been explored over the past decade. We review the more recent literature to recognize studies investigating recent medical and chemotherapeutic agents that have been experienced or are currently being tested for meningiomas. Combination therapies affecting multiple molecular targets are currently opening up and present significant promise as adjuvant therapeutic options. However, there is an evident need for new molecular studies in order to better understand the biology of meningiomas and, thus, to identify new and more specific therapeutic targets.
International Journal of Molecular Sciences · 2023 · 13 citations · open access
Meningiomas and Somatostatin Analogs: A Systematic Scoping Review on Current Insights and Future Perspectives
AbstractMeningioma is the most frequent brain tumor, and the incidence is ever-increasing. Though often benign and slow growth, recurrence rates are substantial and today's surgical and radiation-based treatment are not without complications. No drugs specific for meningiomas are hitherto approved and patients with inoperable or recurrent meningioma are left with few treatment options. Somatostatin receptors are previously detected in meningiomas and may inhibit growth when stimulated by somatostatin. Hence, somatostatin analogs could provide a targeted drug therapy. The aim of this study was to compile the current insights of somatostatin analogs for patients with meningioma. This paper adheres to the PRISMA extension for Scoping Reviews. A systematic search was conducted in the search databases PubMed, Embase via Ovid, and Web of Science. Seventeen papers adhered to the inclusion and exclusion criteria, and critical appraisal was conducted. The overall quality of evidence is low, as none of the studies were randomized or controlled. Various efficacy of somatostatin analogs is reported, and adverse effects are sparse. Due to the beneficial effects reported by some studies, somatostatin analogs may offer a novel last-option treatment for severely ill-patients. Nonetheless, only a controlled study, preferably a randomized clinical trial, could clarify the efficacy of somatostatin analogs.
Light at the end of the tunnel: towards an effective drug therapy for surgery- and radiation-refractory meningioma
AbstractThe vast majority of patients with meningiomas are effectively treated by neurosurgery, radiosurgery and/or radiation therapy. However, there are a small number of patients whose meningiomas recur despite repeated therapies.
In this issue, Drs. Kaley, Wen, and colleagues from four American institutions report the results of a single-arm, multicenter phase II trial with sunitinib in patients with surgery and radiation-refractory atypical (grade II) and anaplastic (grade III) meningiomas (n = 36) as well as an exploratory cohort of 13 patients with recurrent benign (WHO grade I) meningiomas, hemangiopericytomas and hemangioblastomas.1 It is a great and rare moment to participate in the discovery of an effective treatment for patients with previously unmet medical needs. This study describes for the first time that patients with atypical and anaplastic meningiomas without further therapeutic options benefited from therapy with the tyrosine-kinase inhibitor sunitinib. For the first time, a positive result for a prospective study in this setting is reported, fulfilling and even exceeding the predefined efficacy endpoint with an observed rate of 42% of patients remaining progression-free at six months (PFS-6), compared with the predefined efficacy PFS-6 threshold of 30%.
Of note, this was a multicenter investigator-initiated study, emphasizing the rarity of aggressive meningiomas recurring after surgery and radiation. There are indeed only a small number of patients with aggressive meningiomas, meaning that there is low potential for significant sales volumes and thus less interest for drug development by the pharmaceutical industry. Moreover, these patients are frequently symptomatic with headaches, seizures, and a variety of neurological deficits,2 often requiring complex medication regimens for the treatment of pain and the prevention of seizures that could potentially lead to drug interactions. Most patients also have impaired performance status, making their participation in a study even more challenging.
Recently, the Response Assessment in Neuro-Oncology (RANO) working group reviewed the published evidence of medical therapies in patients with surgery- and radiotherapy-refractory meningioma.3 They summarized the experience from 47 publications, including retrospective analyses, pilot and phase II trials, and one phase III trial. Fourteen trials with cytotoxic agents involving a total of 265 patients (most of them with recurrent meningiomas WHO grade I) were reported from 1991 to 2012, eleven of them with hydroxyurea and one each with temozolomide, irinotecan, and with a combination of adriamycin, cyclophosphamide, and vincristine. Six publications reported data on treatment with the somatostatin analogue octreotide, with a median progression-free survival ranging from 5 to 15 months, mainly in patients with WHO grade I meningiomas. Further studies with interferon alpha, hormones, bevacizumab, imatinib, erlotinib, or gefitinib confirmed the poor outcome for patients with aggressive meningiomas and failed to demonstrate any efficacy. The main result of this survey was that it allowed the calculation of a weighted average PFS-6 of 29% for WHO grade I meningiomas and 26% for atypical and anaplastic meningiomas. This survey also showed the commitment of patients participating in all those exploratory trials as well as that of their treating physicians in designing and conducting these studies in order to ameliorate the situation of the affected patients. Searching for druggable targets in aggressive meningiomas,4 Kaley et al. chose sunitinib, an oral tyrosine-kinase inhibitor targeting two pathways involved in meningioma proliferation in vitro, the platelet-derived growth factor receptor (PDGFR) and the vascular endothelial growth factor receptor 2 (VEGFR2), which was found to be upregulated in all meningiomas and whose expression was shown to increase with recurrence.5 Previous retrospective surveys and phase II trials using imatinib to target PDGFR alpha were limited to a small number of patients and failed to demonstrate any efficacy.6–7
In the study reported in this issue, sunitinib was used in the same dosage as for renal cell cancer and this study met its pre-specified endpoint. However, significant toxicity was observed, including one fatal and three additional intracranial hemorrhages, and eleven patients (11/36, 30%) had interruption of therapy because of toxicity. The suggestion of benefit and increased toxicity of sunitinib in meningioma patients contrasts with the relatively good tolerability but lack of efficacy with this agent in patients with recurrent glioblastoma.8 The favorable PFS results with sunitinib are similar to a small retrospective study of bevacizumab in 15 patients with aggressive meningiomas.9
Most interestingly, a correlative imaging study showed a reduction of the intratumoral blood flow in nearly all the patients who were examined. It will be of great interest to correlate these data with the observed therapeutic responses and with the target expression of the respective meningiomas. This study represents a real advance in the management of patients with aggressive meningiomas and will guide further research for these sorely afflicted patients.
AbstractAbstract: Neurosurgeons and their patients frequently confront meningiomas. While some meningiomas can be treated with complete removal and freedom from recurrence, others are difficult to treat for several reasons. Particular locations, recurrent tumors, and pathological subtypes can all complicate the treatment of meningiomas. In an effort to better understand these tumors, a sizable body of literature has evolved describing the biology and basic science of meningiomas. It is hoped that this research will result in better medical and surgical treatment of these tumors. This article reviews the basic science issues currently thought to be important in meningiomas.
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.
