DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial adenomatous polyposis 3 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFamilial adenomatous polyposis 3 maps to a 2-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 familial adenomatous polyposis 3 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
nth like DNA glycosylase 1 (NTHL1) — NTHL1 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 sf4drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7RDS · 2.5 Å · ligand IRON/SULFUR CLUSTER (SF4). Experimental structure, not a prediction.
What the evidence adds up to
A 1996 study of 41 children aged 6 to 16 at risk for familial adenomatous polyposis found that predictive genetic testing did not cause clinically significant psychological symptoms. Nineteen children carried a mutation and 22 did not. Depression, anxiety, behaviour problem and competence scores remained in the normal range three months after testing. Subclinical changes were observed: mutation-positive children with affected mothers had higher depression scores, and children with affected mothers had increased anxiety scores regardless of test result. Parents who were unaffected by polyposis but had both a mutation-positive and a mutation-negative child reported increased depressive symptoms. The authors caution that long-term follow-up may not be equally favourable.
Surgical management is the mainstay for patients who require intervention. A 2017 review states that prophylactic removal of the rectum and colon is often needed, but that sparing the rectum at the first surgery is safe in selected patients. A 2013 Norwegian registry study of 61 patients who had ileal pouch–anal anastomosis compared those who received mucosectomy (39 patients) with those who did not (22 patients). Over a mean follow-up of 15.5 and 13.7 years respectively, adenoma formation at the anastomotic site occurred in 4 of 39 patients with mucosectomy (estimated rate 17%) versus 14 of 22 without (estimated rate 75%, p = 0.0001). One patient without mucosectomy developed a Dukes A cancer at the anastomotic site. Adenoma formation in the ileal pouch itself did not differ significantly between the two procedures (38% in both groups, p = 0.10). The study is retrospective, relies on registry data, has limited numbers, and may be affected by surgeon preference.
A 2012 case report describes a fetal hepatoblastoma detected on ultrasound in a 23-year-old woman. Postnatal biopsy confirmed hepatoblastoma, and maternal thyroid biopsy revealed papillary carcinoma. Genetic testing showed APC gene disruption at 5q22.2 in both neonate and mother. Pedigree analysis revealed multigenerational colon and thyroid cancer, consistent with familial adenomatous polyposis. The authors present this as a novel route to diagnosis.
A 2007 study of six unrelated Turkish families with familial adenomatous polyposis identified three APC gene mutations, two of which were novel: 1018T>C and 1309delGAAAA. The 1018T>C change is a silent mutation that the authors predict may create new exonic splicing enhancer motifs. The study is small and does not report clinical outcomes or response to any intervention.
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 Pediatrics and Adolescent Medicine · 1996 · 85 citations
Genetic Testing for Cancer in Children
AbstractOBJECTIVE: To study the psychological effect of genetic testing in children. DESIGN: We evaluated the psychological effect of predictive genetic testing through surveys of children at risk for familial adenomatous polyposis. Their psychological state was assessed before testing and 3 months later. SETTING: A research clinic. PARTICIPANTS: A volunteer sample of 41 children, aged 6 to 16 years, and their parents. MAIN OUTCOME MEASURES: Self-report inventories of depression, anxiety, behavior problems, and competence. RESULTS: Nineteen children were found to have a gene mutation (mutation-positive) and 22 did not (mutation-negative). Their depression, anxiety, and behavior problem and competence scores remained in the normal range after testing. Also, parents' depression scores remained within normal limits at follow-up. There were subclinical changes, however. Mutation-positive children with affected mothers had significantly higher depression scores at follow-up. Also, regardless of test results, children with affected mothers had significantly increased anxiety scores after testing. In families with mutation-positive and mutation-negative children, familial adenomatous polyposis-unaffected parents experienced significantly increased depressive symptoms at follow-up. CONCLUSIONS: Predictive testing of children at risk for familial adenomatous polyposis did not lead to clinically significant psychological symptoms in tested children or their parents. However, it is premature to conclude that long-term follow-up will be equally favorable. Additional study will be needed to determine the families' understanding of the genetic information and the effect of the information on familial relationships.
ANZ Journal of Surgery · 2017 · 23 citations · open access
Dispelling misconceptions in the management of familial adenomatous polyposis
AbstractPatients with familial adenomatous polyposis require surgical intervention at some point in their lives. The diagnosis is often apparent from their phenotype and family history, however, this is not always the case. Many factors can influence the surgical strategy although the polyposis burden and distribution remain the main consideration. While prophylactic removal of the rectum and colon is often required, sparing the rectum at the index surgery is safe in select patients. This article aims to dispel misconceptions in the diagnosis and treatment of patients with familial adenomatous polyposis.
Diseases of the Colon & Rectum · 2013 · 17 citations
Adenoma Formation and Malignancy After Restorative Proctocolectomy With or Without Mucosectomy in Patients With Familial Adenomatous Polyposis
AbstractBACKGROUND: There is controversy concerning whether or not to perform mucosectomy after IPAA in patients with familial adenomatous polyposis. Although more frequent adenoma formation at the anastomotic site in patients without a mucosectomy is documented, the interpretation of the theoretical reflections and empirical findings are ambiguous. OBJECTIVE: The aim of this study was to assess the differences in adenoma formation at the anastomotic site and in the ileal pouch among patients with familial adenomatous polyposis after IPAA with or without mucosectomy. DESIGN: Data were gathered from The Norwegian Polyposis Registry and The Cancer Registry of Norway. PATIENTS: Sixty-one patients with familial adenomatous polyposis who had IPAA were included in the Norwegian Polyposis Registry. MAIN OUTCOME MEASURES: The frequency of adenoma development in the pouch or at the anastomotic site was measured. RESULTS: Thirty-nine patients had a pelvic pouch performed with mucosectomy and 22 patients without. The observational time was 15.5 and 13.7 years. Adenoma formation at the anastomotic site was 4 in 39 and 14 in 22, and the estimated rate was 17% vs 75% (p = 0.0001). One patient without mucosectomy had a cancer (Dukes A) at the anastomotic site. There was no estimated long-term difference in adenoma formation in the ileal pouches between the 2 surgical procedures (38%) (p = 0.10). LIMITATIONS: The study is retrospective, in part, and relies on data from registries. There is a limited number of cases, and selection bias because of surgeon preference may exist. CONCLUSION: In patients with familial adenomatous polyposis who undergo IPAA, adenoma formation at the anastomotic site is significantly reduced after mucosectomy. Mucosectomy may be the preferable procedure to prevent adenomas at the anastomotic site.
Perinatal Detection of Familial Adenomatous Polyposis
AbstractBACKGROUND: Hepatoblastoma is an uncommon fetal neoplasm that may represent an isolated malignancy or a component of a familial cancer or syndromic diagnosis. CASE: A large fetal liver mass was detected on routine ultrasound examination of a 23-year-old woman with thyroid nodules and hypertension. Inferior vena cava compression prompted delivery; postnatal biopsy revealed hepatoblastoma. Maternal thyroid biopsy revealed papillary carcinoma. Neonatal and maternal cytomolecular analysis revealed APC gene disruption at 5q22.2. Pedigree analysis exposed multigenerational colon cancer and thyroid cancer, which in conjunction with genetic testing is consistent with familial adenomatous polyposis. CONCLUSION: This is a novel means of familial adenomatous polyposis diagnosis. Obstetricians and perinatologists should be alert for familial cancer or syndromic diagnoses presenting as fetal neoplasms.
Diseases of the Colon & Rectum · 2007 · 0 citations
The Mutation Spectrum of the APC Gene in Turkish Patients with Familial Adenomatous Polyposis
AbstractPURPOSE: Familial adenomatous polyposis, an autosomal-dominant disease characterized by the presence of 100 or more colorectal adenomatous polyps, results from mutations in the adenomatous polyposis coli tumor suppressor gene. This study was designed to investigate adenomatous polyposis coli gene mutations in members of Turkish families with familial adenomatous polyposis to constitute an adenomatous polyposis coli mutation spectrum for the Turkish population and to determine specific biomarkers for use in the early diagnosis of familial adenomatous polyposis. METHODS: We investigated adenomatous polyposis coli gene mutations in six unrelated families with familial adenomatous polyposis by using heteroduplex analysis and DNA sequencing. RESULTS: We identified three different mutations in six families. Of these one is known and two are novel: 1018T>C and 1309delGAAAA. The mutation of a T to C transversion at codon 1018 does not cause an alteration in the meaning of the codon; however, it was determined that this silent mutation does cause the formation of new exonic splicing enhancers (ESEs) motifs on a mutated sequence by using ESEfinder program. CONCLUSIONS: This study contributes to enlarging the adenomatous polyposis coli gene mutations spectrum and to defining new biomarkers for the early diagnosis of Turkish patients with familial adenomatous polyposis.
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.
