DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Lynch syndrome 8 — 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 moduleLynch syndrome 8 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 lynch syndrome 8 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
epithelial cell adhesion molecule (EPCAM) — EPCAM 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 dmudrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4MZV · 1.865 Å · ligand DECYL-BETA-D-MALTOPYRANOSIDE (DMU). Experimental structure, not a prediction.
What the evidence adds up to
About 2% of all colorectal cancer occurs in the context of Lynch syndrome, an autosomal dominant condition caused by mutations in mismatch repair genes. A systematic review of evidence published between 1996 and 2006 found that colonoscopic surveillance for individuals with Lynch syndrome is supported by evidence, though the optimal age to start and frequency of examinations remain unresolved. The review recommended colonoscopy every one to two years starting at ages 20 to 25, or age 30 for those with MSH6 mutations, or ten years younger than the youngest age of diagnosis in the family. The same review acknowledged an absence of demonstrated efficacy for annual endometrial sampling with transvaginal ultrasound, urinalysis with cytology, and history and examination, but still recommended them. For individuals undergoing surgical resection of colon cancer, subtotal colectomy was favoured, and evidence supported prophylactic hysterectomy and oophorectomy.
The long-studied family G, first documented in 1895 and updated through 2000, now includes 929 known descendants. Cancers of the colon and rectum (standardised incidence ratio 3.20, 95% confidence interval 2.39 to 4.19) and endometrium (SIR 3.51, 95% CI 1.92 to 5.89) continue to predominate. Five of 40 tested members carried the MSH2 T to G mutation, placing 15 living relatives at increased risk, while 97 living members could be excluded as mutation carriers. Molecular diagnostic testing has transformed care for families in which a pathogenic mutation has been identified.
In a Malay cohort of 17 patients selected by Bethesda criteria, 41% (n=7) had abnormal immunohistochemical staining for one or more mismatch repair proteins. Loss of expression was noted in 13 tumour tissues: four showed loss of MLH1, five loss of PMS2, and two each loss of MSH2 and MSH6. The study concluded that revised Bethesda criteria and immunohistochemical analysis constitute a convenient first-line screening approach for Lynch syndrome in Malay cohorts.
What is still missing is prospective trial data that resolves the optimal age and interval for colonoscopic surveillance, and any randomised evidence that the recommended non-colonoscopic screening tests reduce mortality. The systematic review explicitly noted the absence of demonstrated efficacy for those tests. No drug intervention for Lynch syndrome appears in these abstracts; the focus remains entirely on screening, surgical prevention, and molecular diagnosis. Funding for large, long-term trials of surveillance strategies and for studies that can stratify patients by specific mutation type and family history is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PubMed · 2006 · 633 citations
Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review.
AbstractCONTEXT: About 2% of all colorectal cancer occurs in the context of the autosomal dominantly inherited Lynch syndrome, which is due to mutations in mismatch repair genes. Potential risk-reducing interventions are recommended for individuals known to have these mutations. OBJECTIVES: To review cancer risks and data on screening efficacy in the context of Lynch syndrome (hereditary nonpolyposis colorectal cancer) and to provide recommendations for clinical management for affected families, based on available evidence and expert opinion. DATA SOURCES AND STUDY SELECTION: A systematic literature search using PubMed and the Cochrane Database of Systematic Reviews, reference list review of retrieved articles, manual searches of relevant articles, and direct communication with other researchers in the field. Search terms included hereditary non-polyposis colon cancer, Lynch syndrome, microsatellite instability, mismatch repair genes, and terms related to the biology of Lynch syndrome. Only peer-reviewed, full-text, English-language articles concerning human subjects published between January 1, 1996, and February 2006 were included. The US Preventive Services Task Force's 2-tier system was adapted to describe the quality of evidence and to assign strength to the recommendations for each guideline. EVIDENCE SYNTHESIS: The evidence supports colonoscopic surveillance for individuals with Lynch syndrome, although the optimal age at initiation and frequency of examinations is unresolved. Colonoscopy is recommended every 1 to 2 years starting at ages 20 to 25 years (age 30 years for those with MSH6 mutations), or 10 years younger than the youngest age of the person diagnosed in the family. While fully acknowledging absence of demonstrated efficacy, the following are also recommended annually: endometrial sampling and transvaginal ultrasound of the uterus and ovaries (ages 30-35 years); urinalysis with cytology (ages 25-35 years); history, examination, review of systems, education and genetic counseling regarding Lynch syndrome (age 21 years). Regular colonoscopy was favored for at-risk persons without colorectal neoplasia. For individuals who will undergo surgical resection of a colon cancer, subtotal colectomy is favored. Evidence supports the efficacy of prophylactic hysterectomy and oophorectomy. CONCLUSIONS: The past 10 years have seen major advances in the understanding of Lynch syndrome. Current recommendations regarding cancer screening and prevention require careful consultation between clinicians, clinical cancer genetic services, and well-informed patients.
History and Molecular Genetics of Lynch Syndrome in Family G
AbstractCONTEXT: In 1895, Aldred Scott Warthin, MD, PhD, initiated one of the most thoroughly documented and longest cancer family histories ever recorded. The unusually high incidence and segregation of cancers of the colon, rectum, stomach, and endometrium in Dr Warthin's family G was later followed up by his colleagues, most recently by Henry Lynch, MD. Described today as a Lynch syndrome family, family G was last documented in 1971, prior to the modern era of molecular diagnostics. OBJECTIVE: To update family G. DESIGN, SETTING, AND PARTICIPANTS: Historical prospective cohort study of family G members from 1895 to 2000. MAIN OUTCOME MEASURES: The primary outcomes were the frequencies and types of cancers, ages at diagnosis, and presence of the T to G transversion at the splice acceptor site of exon 4 of the mutS homolog 2, colon cancer, nonpolyposis type 1 (E coli) (MSH2) gene in family G members. A secondary analysis compared cancer-specific incidence rates in family G with published national and regional cancer incidence rates through the standardized incidence ratio (SIR). RESULTS: Family G now has 929 known descendants of the original progenitor first reported in 1913. Cancers of the colon and rectum (SIR, 3.20; 95% confidence interval [CI], 2.39-4.19) and endometrium (SIR, 3.51; 95% CI, 1.92-5.89) continue to predominate in family G. Five of 40 tested members of family G carry the MSH2 T to G mutation; as a result, 15 of their living relatives are at increased risk of developing 1 or more colorectal or Lynch syndrome-associated cancers. In contrast, 97 living members of family G can now be excluded as mutation carriers. CONCLUSION: Within the last decade, molecular diagnostic testing has transformed the care of family G and other Lynch syndrome families in which a pathogenic mutation has been identified.
Asian Pacific Journal of Cancer Prevention · 2015 · 4 citations · open access
Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening
AbstractBACKGROUND: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry. MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2. RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively. CONCLUSIONS: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.
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.
