DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for glioblastoma multiforme — screening already-approved drugs against its 50-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGlioblastoma multiforme maps to a 50-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
approvedRegorafenibApproved drugapprovedSorafenibApproved drug
Structures already discussed alongside glioblastoma multiforme in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Human P38 MAP kinase — Sorafenib has a real, experimentally solved structure in complex with this target (PDB 3GCS, 2.1 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 baxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3GCS · 2.1 Å · ligand Sorafenib (BAX). Experimental structure, not a prediction.
What the evidence adds up to
Glioblastoma multiforme remains one of the most lethal and treatment-resistant human tumours. Among surgery, radiation therapy, and chemotherapy, only radiation therapy has been shown to improve survival. Despite thirty years of intensive efforts to find an effective chemotherapy regimen, median survival has not changed appreciably since the introduction of radiation therapy and remains 12 to 15 months. The tumour invariably recurs, and at recurrence few treatment options exist, often with limited effectiveness.
Sorafenib was given to 30 patients with recurrent or progressive high-grade glioma, 16 of whom had glioblastoma multiforme. All but one had received previous standard multimodal treatment, and 18 patients (60%) had received more than one line of chemotherapy. Median progression-free survival was 3 months (95% CI 1.9–4.1 months) in glioblastoma patients and 3.1 months (95% CI 1.4–4.8 months) in other high-grade gliomas. Progression-free survival at six months for the whole cohort was 23%. Median overall survival after starting sorafenib was 6 months (95% CI 3.9–8.0 months) for glioblastoma patients. Sixteen patients reported adverse events, mostly moderate; one patient died of cerebral bleeding. The authors concluded that sorafenib monotherapy was associated with tumour stabilisation in a small subset of heavily pretreated patients.
Regorafenib was studied in 56 elderly patients (over 60 years) with recurrent glioblastoma in a real-life retrospective analysis. Median progression-free survival was 4.1 months and median overall survival was 6.8 months. Age did not significantly influence progression-free survival. Median overall survival was 7.7 months in MGMT-methylated patients versus 5.6 months in unmethylated patients. Both overall and progression-free survival were longer in IDH-mutant patients. The results were in line with the REGOMA trial, a phase 2 study in which regorafenib showed a statistically significant improvement in median overall survival compared with lomustine. A single case report described a 43-year-old patient treated with regorafenib in third line who achieved good disease control and long progression-free survival.
What is still missing are prospective, randomised trials large enough to confirm these signals in defined subgroups, particularly for elderly patients and for those with specific methylation or mutation status. The cellular and molecular heterogeneity of glioblastoma, its high proliferation rate, pervasive infiltration, and therapeutic resistance remain fundamental obstacles. No confirmed standard treatment exists for recurrent glioblastoma, and the risk-benefit ratio of any agent must be weighed against the uniformly fatal prognosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 2006 · 62 citations
Treatment of Glioblastoma Multiforme
AbstractGlioblastoma multiforme is one of the most lethal and treatment-resistant of human tumors. Among the therapeutic triad of surgery, radiation therapy, and chemotherapy, only radiation therapy has been shown to improve survival.1 Despite 30 years of intensive efforts to find an effective chemotherapy regimen for glioblastoma multiforme, the median survival of 12 to 15 months has not changed appreciably since the introduction of radiation therapy.
Sorafenib for patients with pretreated recurrent or progressive high-grade glioma
AbstractTherapeutic options for patients with pretreated advanced high-grade glioma (HGG) are limited. Sorafenib, a small molecule with multiple potential beneficial actions, appears particularly promising. We reviewed the outcomes of 30 patients with recurrent or progressive HGG treated with sorafenib within a named patient program. Overall, 16 patients suffered from recurrent or progressive glioblastoma multiforme and 14 patients had grade 3 gliomas. All but four patients had previously undergone surgical debulking; all but one patient had received previous standard multimodal treatment; and 18 patients (60%) had received more than one line of chemotherapy, in median three. Progression-free survival (PFS), defined as the time from initiation of sorafenib to treatment discontinuation because of tumor progression or death, was selected as the endpoint. The use of sorafenib resulted in a median PFS of 3 months [95% confidence interval (CI) 1.9-4.1 months] in patients with glioblastoma and of 3.1 months (95% CI 1.4-4.8 months) in patients with other HGG. The PFS-6 for the whole cohort was 23%. Sixteen patients reported adverse events, mostly moderate, with hypertension as the most frequently reported toxicity (seven patients). One patient died of cerebral bleeding (grade 5 toxicity). The overall survival after initiation of sorafenib was 6 months (95% CI 3.9-8.0 months) for patients with glioblastoma multiforme and 10 months (95% CI 3.1-16.9 months) for patients with HGG. In this retrospective analysis of heavily pretreated patients with HGG, sorafenib monotherapy was associated with tumor stabilization in a small subset of patients. The risk-benefit ratio was acceptable in the context of an apparent clinical benefit in patients with a fatal disease.
Molecular and Clinical Oncology · 2023 · 11 citations · open access
Clinical activity of regorafenib in elderly patients with recurrent glioblastoma
AbstractGlioblastoma multiforme is one of the most frequent and aggressive primary tumors in the central nervous system, representing >60% of all brain tumors in adults. Despite treatment, prognosis remains poor with most if not all patients experiencing disease recurrence and a 2-year survival rate of 27%. At present, no confirmed standard treatment exists for recurrent glioblastoma. Regorafenib is one of the few options available, based on results from the REGOMA trial. In the present study, a real-life retrospective investigation on the role of regorafenib in patients with recurrent glioblastoma (>60 years old) from two main Oncological Units in South Italy (Azienda Ospedaliera Universitaria Luigi Vanvitelli, Naples, Italy and Ospedale Civile San Giovanni di Dio, Frattamaggiore, Naples, Italy), was performed. The primary endpoint was overall survival (OS), whereas progression-free survival (PFS), objective response rate and disease control were secondary endpoints. Survival was then analyzed according to age, isocitrate dehydrogenase (IDH) and methylated methylguanine-DNA-methyltransferase (MGMT) status. A total of 56 patients met the eligibility criteria. The intention to treat population median PFS (mPFS) was 4.1 months and median OS (mOS) was 6.8 months. Age did not appear to have a significant influence on mPFS. mOS in MGMT-methylated patients was improved compared with that of the unmethylated group (7.7 months vs. 5.6 months). Both mOS and mPFS were longer in IDH-mutant patients. The present study was one of the first real life analyses of regorafenib in recurrent glioblastoma. The results were in line with the REGOMA trial. Age did not appear to be a prognostic factor, thus suggesting that treatment choice should not be different in elderly. MGMT methylation appeared to influence OS. To the best of our knowledge, this was the first report of regorafenib activity in older patients and, while the results were statistically significant, these should be confirmed in further studies.
Case Reports in Oncology · 2022 · 7 citations · open access
Regorafenib beyond the Second Line in Relapsed Glioblastoma: A Case Report and Literature Review
AbstractGlioblastoma multiforme (GBM) is one of the most frequent and aggressive primary tumors in the central nervous system, representing more than 60% of all brain tumors in adults. Primary GBM remains incurable with a poor prognosis both for limited therapeutic alternatives and for a high risk of progression or recurrence. In fact, at recurrence, the few treatment options available, and often characterized by limited effectiveness, have always been an Achilles' heel. The recent approval of second line of regorafenib, a multikinase inhibitor, has given hope after several years of darkness for new therapies in the treatment of GBM. Indeed, in the REGOMA trial, a phase 2 study, regorafenib was the first drug to show a statistically significant improvement in median overall survival compared with lomustine group, usually used in the second-line treatment after temozolomide failure. We report a case of a 43-year-old patient affected by GBM in treatment with regorafenib in third line of therapy with good disease control and long PFS.
Cross-talk between tumor stem cells and tumor cells: a glioblastoma strategy to promote malignancy
AbstractGlioblastoma multiforme (GBM) is the most frequent and malignant type of primary tumors of the central nervous system. Despite current advances in multimodal therapies, involving advanced surgery, radio- and chemotherapy, and the development of innovative targeted therapies the outcome for patients with GBM is nearly always fatal, with a median survival time of only 12–15 months (1). Various obstacles hamper development of effective therapies, including cellular and molecular heterogeneity, high proliferation rate, pervasive tumor cell infiltration, intensive angiogenesis, therapeutic resistance, and, not last, the lack of a full understanding of the pathobiology of the disease.
Peripheral biomarkers in glioblastoma patients—is it all just HOTAIR?
AbstractGlioblastoma multiforme is the most aggressive form of brain cancer. The standard of care treatment for newly diagnosed patients with glioblastoma is tumour de-bulking by surgery, followed combination therapy consisting of radiation and temozolomide chemotherapy (1). The tumour invariably recur, often in the same area or adjacent to as the original surgical-resected tumor (2,3).
DDEL-19PENETRATION OF HOMING PEPTIDE-FUNCTIONALIZED NANOPARTICLES TO GLIOMA SPHEROIDS IN VITRO
AbstractGlioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain malignancy. Even when subjected to multimodal treatment using surgery, chemo- and radiotherapy, the majority of GBM patients die within a year after diagnosis. Affinity targeting of anti-glioma drugs to malignant lesions, in particular to disseminated cells hiding behind the blood-brain-barrier, may dramatically improve efficacy of antiglioma therapies. Upon intravenous administration, tumor penetrating peptides (TPP-s) home to malignant lesions and extravasate into tumor parenchyma. Interestingly, these peptides retain their activity to penetrate excised tumor explants in short-term ex vivo assays. Here, we report development of an in vitro 3D penetration assay of homing peptide-functionalized silver nanoparticles (AgNP) in U87 glioma spheroids. U87 spheroids were incubated with fluorescent silver nanoparticles functionalized with prototypic tumor penetrating peptides, iRGD (CRGDKGPDC) and RPARPAR, or control peptides. Subsequently, spheroids were incubated with a non-toxic etching solution that selectively removes the extracellular AgNP with no effect on internalized AgNP. Fluorescence imaging and Matlab -based quantitative analysis of spheroid cryosections and of live spheroids was used to assess distribution of AgNP with and without etching treatment. Compared to control nanoparticles, iRGD and RPARPAR functionalized AgNP showed dramatically increased binding and penetration of the particles in the U87 spheroids. The binding was inhibited by peptide receptor-blocking anti NRP-1 and anti-av-integrin antibodies (but not by control antibodies), suggesting specific effect of AgNP surface peptides. Establishment and validation of 3D in vitro tumor spheroid penetration assay may provide a standardized system for evaluation tumor homing and penetration ability of homing peptides and to allow medium- throughput mechanistic and experimental therapy studies.
Glioblastoma: Prognostic Factors and Predictive Response to Radio and Chemotherapy
AbstractGlioblastoma multiforme (GBM) is characterized by poor prognosis despite an aggressive therapeutic strategy. In recent years, many advances have been achieved in the field of glioblastoma biology. Here we try to summarize the main clinical and biological factors impacting clinical prognostication and therapy of GBM patients. From that standpoint, hopefully, in the near future, personalized therapies will be available.
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.
