DeCure for Desmoid tumor caused by somatic mutation
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for desmoid tumor caused by somatic mutation — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDesmoid tumor caused by somatic mutation maps to a 1-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 desmoid tumor caused by somatic mutation 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
catenin beta 1 (CTNNB1) — CTNNB1 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 prodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8Z10 · 2.35 Å · ligand PROLINE (PRO). Experimental structure, not a prediction.
What the evidence adds up to
In 145 sporadic desmoid tumour specimens, 73% carried a CTNNB1 (β-catenin) mutation. Among 115 patients who had a macroscopically complete surgical resection, 75% had such a mutation. The most common mutations were T41A (46%) and S45F (25%). At a median follow-up of 31 months, 5-year recurrence-free survival was 58% for patients with mutated tumours and 74% for those with wild-type tumours; this difference was not statistically significant. The specific codon mutation did not correlate with recurrence risk. The study did not detect a statistically significant difference in recurrence according to either CTNNB1 mutation status or the specific mutation.
A separate case report of a 2-year-old girl with familial adenomatous polyposis and a rapidly enlarging forehead tumour found that the tumour had desmoid features on microscopy. Cytogenetic analysis showed loss of chromosome region 5(q21q22). A truncating APC gene mutation was identified in the child’s leukocyte DNA and in her affected father. Linked DNA markers suggested the tumour had lost the maternal wild-type allele, and a mutation-induced restriction site alteration demonstrated hemizygosity of the mutant sequence in the tumour DNA. The authors concluded that a “second hit” inactivation of the APC gene was present.
In a genomic analysis using a high-density SNP array in 9 patients, single samples showed numerical aberrations on chromosomes 20 and 6 (trisomy 20 or monosomy 6). No trisomy 8 was detected. Recurrent heterozygous deletions were found in chromosome 5q (including the APC gene locus, n=3) and chromosome 8p23 (n=4, containing coding regions for the potential tumour suppressor gene CSMD1). This novel deletion in 8p23 showed an association with local recurrence. Structural changes (gain of chromosomes 8 and 20) were found in a minority of cases.
What is still missing is a prospective trial that stratifies patients by CTNNB1 mutation type or by the 8p23 deletion, and that tests a specific drug in a defined molecular subgroup. The available data are retrospective, from small or mixed cohorts, and do not provide evidence that any drug alters recurrence or progression. No randomised controlled trial of a targeted agent in mutation-defined desmoid tumours has been reported. Funding for such a trial, and for the necessary molecular screening to identify eligible patients, remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Oncologist · 2013 · 132 citations · open access
β-Catenin Mutation Status and Outcomes in Sporadic Desmoid Tumors
AbstractBACKGROUND: Mutations in the gene-encoding β-catenin, CTNNB1, are highly prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We sought to determine the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoid tumors and to determine whether CTNNB1 mutation status correlates with disease outcome. METHODS: Single-base extension genotyping of the CTNNB1 gene was performed on 145 sporadic, paraffin-embedded desmoid tumor specimens. Correlation of mutation status with outcome was performed on a subset of 115 patients who underwent macroscopically complete surgical resection. RESULTS: CTNNB1 mutations were detected in 106 of 145 (73%) tumor specimens and in 86 of 115 (75%) specimens from patients who underwent curative-intent surgical resection, including discrete mutations in the following codons of CTNNB1 exon 3: T41A (46%), S45F (25%), S45P (1.7%), and S45C (0.9%). Desmoid tumors of the superficial trunk were significantly less likely to harbor CTNNB1 mutations than tumors located elsewhere, but none of the other examined clinicopathologic factors were found to be associated with CTNNB1 mutation status. At a median follow-up of 31 months, 5-year recurrence-free survival was slightly, although not statistically significantly, worse for patients with β-catenin-mutated tumors than for those with wild-type tumors (58% vs. 74%, respectively). The specific CTNNB1 codon mutation did not correlate with the risk for recurrence. CONCLUSION: CTNNB1 mutations are indeed common in sporadic desmoid tumors. However, our study did not detect a statistically significant difference in recurrence risk according to either the CTNNB1 mutation status or the specific CTNNB1 mutation.
Cranial desmoid tumor associated with homozygous inactivation of the adenomatous polyposis coli gene in a 2‐year‐old girl with familial adenomatous polyposis
AbstractBACKGROUND: Familial adenomatous polyposis (FAP) is a dominantly inherited disorder characterized by the presence of more than 100 adenomatous polyps in the colon and rectum starting in the second decade of life. FAP is associated with extra colonic manifestations, including desmoid tumors. METHODS: A 2-year-old girl presented with a rapidly enlarging tumor of the forehead and a family history of FAP. The tumor was cultured for cytogenetic studies. A DNA linkage study using flanking and intragenic polymorphisms of the adenomatous polyposis coli (APC) gene was performed to identify the allele loss in the tumor. Germline mutation identification was by single strand conformation polymorphism analysis of exon 15 of the APC gene, with subsequent double stranded sequencing of fragments with conformational changes. A mutation-induced loss of a restriction site was used to confirm allele loss in the tumor. RESULTS: Microscopically, the tumor had desmoid features. Cytogenetic analysis of the tumor demonstrated loss of chromosome region 5(q21q22). A truncating adenomatous polyposis coli (APC) gene mutation was identified in the leukocyte DNA from the child and her affected father. Linked DNA markers suggested that the tumor had lost the maternal, wild-type allele. A mutation-induced restriction endonuclease site alteration demonstrated hemizygosity of the mutant sequence in the tumor DNA. CONCLUSIONS: These findings are compatible with the presence of a "second hit" inactivation of the APC gene and implicate this gene in the pathogenesis of desmoid tumors.
Oncology Research and Treatment · 2012 · 3 citations · open access
Molecular Analysis of Desmoid Tumors with a High-Density Single-Nucleotide Polymorphism Array Identifies New Molecular Candidate Lesions
AbstractBACKGROUND: Desmoid tumors are neoplastic proliferations of connective tissues. The mutation status of the gene coding for catenin (cadherin-associated protein) beta 1 (CTNNB1) and trisomy 8 on the chromosomal level have been described to have prognostic relevance. PATIENTS AND METHODS: In order to elucidate new molecular mechanisms underlying these tumors, we carried out a molecular analysis with a genome-wide human high-density single-nucleotide polymorphism (SNP) array, in 9 patients. RESULTS: Single samples showed numerical aberrations on chromosomes (Chrs) 20 and 6 with either trisomy 20 or monosomy 6. No trisomy 8 could be detected. Recurrent heterozygous deletions were found in Chr 5q (including the APC gene locus, n = 3) and Chr 8p23 (n = 4, containing coding regions for the potential tumor suppressor gene CSMD1). This novel deletion in 8p23 showed an association with local recurrence. In addition, structural chromosomal changes (gain of Chrs 8 and 20) were found in a minority of cases. CONCLUSION: The genomic alteration affecting the candidate gene CSMD1 could be important in the development of desmoid tumors.
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.
