DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Craniopharyngioma — screening already-approved drugs against its 10-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCraniopharyngioma maps to a 10-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
approvedDabrafenibApproved drugapprovedVemurafenibApproved drug
Structures already discussed alongside craniopharyngioma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Human leucine zipper- and sterile alpha motif-containing kinase (ZAK, MLT, HCCS-4, MRK, AZK, MLTK) — Vemurafenib has a real, experimentally solved structure in complex with this target (PDB 5HES, 2.14 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 032drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5HES · 2.14 Å · ligand Vemurafenib (032). Experimental structure, not a prediction.
What the evidence adds up to
Craniopharyngioma is a benign tumour that tends to recur after excision, and its involvement of vital brain structures means that alternatives to radical surgery, such as limited surgery followed by radiotherapy, are often considered. Complete resection on first encounter can be curative but may be impeded by risks to neurovascular structures, and recurrent tumours are frequently refractory to additional surgery and adjuvant radiation or chemotherapy. In a case series of four patients with recurrent craniopharyngioma treated with two courses of fractionated radiation therapy, three attained disease control at a median follow-up of 33 months after reirradiation; one patient developed progressive disease 27 months after reirradiation. Vision remained stable or improved in three evaluable patients, and no additional endocrine toxicities were observed apart from one patient who developed hypothyroidism after treatment.
Two histological subtypes are defined by distinct molecular profiles. Adamantinomatous craniopharyngiomas (ACPs) carry mutations of β-catenin causing Wnt activation with alterations of the MEK/ERK pathway in the great majority of patients; specific alterations also stratify patients to a more aggressive behaviour. Papillary craniopharyngiomas (PCPs) show primary activation of the Ras/Raf/MEK/ERK pathway secondary to BRAF-V600E mutations in most cases. BRAF inhibitors such as dabrafenib or vemurafenib, alone or combined with MEK inhibitors trametinib and cobimetinib, have been given to patients with PCPs and have produced clinically useful and, in some cases, sustained responses. For ACPs, drugs targeting β-catenin and its downstream MAPK pathway have so far only been used in in vitro studies.
Despite the identification of CTNNB1 mutations in ACP and much progress in understanding the molecular pathways disrupted in its pathogenesis, this understanding has not yet translated into tangible patient benefit. The development of novel techniques and preclinical models now provides an opportunity to begin to support treatment decisions and develop new therapeutics based on molecular pathology. The rapid translation of genomic findings to medical therapies for recurrent craniopharyngiomas serves as a roadmap for other neurooncological diseases, but more studies including a larger number of carefully selected patients are required to evaluate the response to currently available and evolving agents alone and in combination.
What is still missing are larger prospective studies with longer follow-up, particularly for reirradiation and for targeted agents in ACP, where no clinical trial data exist. Patient stratification by molecular subtype is now possible but has not been systematically applied in trials, and the financial and organisational support for such trials in a rare disease remains limited.
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 Pediatrics · 2007 · 163 citations
Craniopharyngioma: modern concepts in pathogenesis and treatment
AbstractPURPOSE OF REVIEW: Craniopharyngioma is a benign tumour. Its tendency to recur after excision and the high surgical risk due to involvement of the most vital structures of the brain mean that alternatives to radical surgery should be considered, namely limited surgical procedures followed by radiotherapy. Since both options present inherent risks, optimal craniopharyngioma treatment remains controversial. This paper aims to critically review the recent literature on craniopharyngioma. RECENT FINDINGS: The management of children with craniopharyngioma has benefited from concerted efforts by national and international groups to improve outcome and reduce morbidity. From the current literature it is evident that there is a trend to better integrate all treatment modalities available, tailoring therapies to specific risk factors. Modern imaging and new surgical and radiotherapy techniques are increasing the possibility of cure. Biological markers are under investigation and this will increase our knowledge on craniopharyngioma. SUMMARY: Studies on treatment, biology and pathogenesis of craniopharyngioma, available in the current literature, grew considerably in the last year. Although a consensus has not been reached on all aspects of this complex disease, there is a trend in the field to move quickly towards a better understanding of the disease to improve treatment strategies and to produce clinical cooperative trials.
Neurosurgical FOCUS · 2016 · 49 citations · open access
Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice
AbstractSince the first identification of CTNNB1 mutations in adamantinomatous craniopharyngioma (ACP), much has been learned about the molecular pathways and processes that are disrupted in ACP pathogenesis. To date this understanding has not translated into tangible patient benefit. The recent development of novel techniques and a range of preclinical models now provides an opportunity to begin to support treatment decisions and develop new therapeutics based on molecular pathology. In this review the authors summarize many of the key findings and pathways implicated in ACP pathogenesis and discuss the challenges that need to be tackled to translate these basic science findings for the benefit of patients.
The Journal of Clinical Endocrinology & Metabolism · 2019 · 46 citations · open access
The Medical Therapy of Craniopharyngiomas: The Way Ahead
AbstractCONTEXT: Craniopharyngiomas, which are categorized as adamantinomatous (ACPs) or papillary (PCPs), have traditionally been treated with surgery and/or radiotherapy, although when the tumors progress or recur, therapeutic possibilities are very limited. Following recent advances in their molecular pathogenesis, new medical therapeutic options have emerged. EVIDENCE ACQUISITION: The search strategy that we selected to identify the appropriate evidence involved the following medical subject headings (MeSH) terms: ("Craniopharyngioma" [MeSH] AND "Craniopharyngioma/drug therapy" [MeSH]) NOT ("review" [Publication Type] OR "review literature as topic" [MeSH Terms] OR "review" [All Fields]) AND ("2009/05/01" [PDat]: "2019/04/28" [PDat]). EVIDENCE SYNTHESIS: Mutations of β-catenin causing Wnt activation with alterations of the MEK/ERK pathway are encountered in the great majority of patients with ACPs; specific alterations also stratify patients to a more aggressive behavior. In most PCPs there is primary activation of the Ras/Raf/MEK/ERK pathway secondary to BRAF-V600E mutations. BRAF inhibitors, such as dabrafenib or vemurafenib, either alone or in combination with the MEK inhibitors trametinib and cobimetinib, have been administered to patients with PCPs producing clinically useful and, in some cases, sustained responses. In contrast to PCPs, drugs targeting β-catenin and its downstream MAPK pathway in ACPs have so far only been used in in vitro studies, but there appear to be promising new targets clinically. CONCLUSIONS: The identification of specific genetic alterations in patients with craniopharyngiomas has expanded the therapeutic options, providing evidence for a customized approach using newer molecular agents. More studies including a larger number of carefully selected patients are required to evaluate the response to currently available and evolving agents alone and in combination.
Neurosurgical FOCUS · 2018 · 32 citations · open access
Craniopharyngioma: a roadmap for scientific translation
AbstractOBJECTIVE Craniopharyngiomas are among the most challenging of intracranial tumors to manage because of their pattern of growth, associated morbidities, and high recurrence rate. Complete resection on initial encounter can be curative, but it may be impeded by the risks posed by the involved neurovascular structures. Recurrent craniopharyngiomas, in turn, are frequently refractory to additional surgery and adjuvant radiation or chemotherapy. METHODS The authors conducted a review of primary literature. RESULTS Recent advances in the understanding of craniopharyngioma biology have illuminated potential oncogenic targets for pharmacotherapy. Specifically, distinct molecular profiles define two histological subtypes of craniopharyngioma: adamantinomatous and papillary. The discovery of overactive B-Raf signaling in the adult papillary subtype has led to reports of targeted inhibitors, with a growing acceptance for refractory cases. An expanding knowledge of the biological underpinnings of craniopharyngioma will continue to drive development of targeted therapies and immunotherapies that are personalized to the molecular signature of each individual tumor. CONCLUSIONS The rapid translation of genomic findings to medical therapies for recurrent craniopharyngiomas serves as a roadmap for other challenging neurooncological diseases.
Neurosurgical FOCUS · 2010 · 30 citations · open access
Molecular pathogenesis of craniopharyngioma: switching from a surgical approach to a biological one
AbstractCraniopharyngioma has long been considered a benign tumor because of its pathological aspect. This primordial view of craniopharyngioma fit with the primitive treatment attempts based on blind resection of the tumor each time it recurred. The limits of this management strategy were proven early by the high morbidity related to the resection and recurrence risk despite radical lesion removal. Nowadays, craniopharyngioma must be considered a complex molecular disease, and a detailed explanation of the mechanisms underlying its aggressive biological and clinical behavior, despite some benign pathological features, would be the first step toward defining the best management of craniopharyngioma. Indeed, advances in the knowledge of the molecular mechanisms at the base of craniopharyngioma oncogenesis will lead to comprehension of the critical checkpoints involved in neoplastic transformation. The final research target will be the definition of new biological agents able to reverse the neoplastic process by acting on these critical checkpoints. This biological approach will lead to a refined therapy combining higher efficacy and safety with lower morbidity. In this paper the authors reveal state-of-the-art comprehension of the molecular biology of craniopharyngioma and the consequent therapeutic implications.
Advances in Radiation Oncology · 2020 · 8 citations · open access
Reirradiation for recurrent craniopharyngioma
AbstractPURPOSE: Reirradiation is rarely administered to patients with recurrent craniopharyngioma owing to concerns regarding visual and endocrine side effects. The purpose of this case series was to evaluate our institutional experience of patients with craniopharyngioma treated with 2 courses of fractionated radiation therapy. METHODS AND MATERIALS: A retrospective study was performed of all patients with craniopharyngioma treated with 2 courses of fractionated radiation therapy at a single institution. Electronic medical records and radiation therapy records were reviewed. RESULTS: We identified 4 eligible patients with recurrent craniopharyngioma. With a median follow-up of 33 months after reirradiation, 3 patients attained disease control; 1 patient developed progressive disease, 27 months after reirradiation. In 3 evaluable patients, vision remained stable or improved after reirradiation; one patient had no light perception before reirradiation. None of the patients experienced additional endocrine toxicities after reirradiation, apart from one patient who had low serum thyroid stimulating hormone before reirradiation and later developed hypothyroidism after treatment. CONCLUSIONS: Reirradiation may represent a safe and effective therapeutic option for selected patients with recurrent, refractory craniopharyngioma and without other salvage treatment options. Larger studies with longer-term follow up are warranted to better understand outcomes in these patients.
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.
