DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Lynch syndrome — screening already-approved drugs against its 27-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 maps to a 27-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 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
transforming growth factor beta receptor 2 (TGFBR2) — TGFBR2 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 6-methoxypyridin-3-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5QIN · 1.57 Å · ligand N-{4-[3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide (J2V). 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 is supported for individuals with Lynch syndrome, though the optimal age to start and frequency of examinations remained unresolved. Colonoscopy was recommended 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 review noted that while there was no demonstrated efficacy, annual endometrial sampling and transvaginal ultrasound of the uterus and ovaries from ages 30 to 35, annual urinalysis with cytology from ages 25 to 35, and annual history, examination, and genetic counselling from age 21 were also recommended. For individuals undergoing surgical resection of colon cancer, subtotal colectomy was favoured, and evidence supported the efficacy of prophylactic hysterectomy and oophorectomy.
A 2019 study analysed the PMS2 gene in 64 Lynch syndrome families and identified several genetic variants, including three novel variants of unknown significance. The carriers of these novel variants also carried other variants in the PMS2 gene or in other mismatch repair genes. The authors suggested these novel PMS2 variants might act in an additive manner to manifest the Lynch syndrome phenotype, but no efficacy data or clinical outcomes were reported.
A 1986 preliminary report on gastrointestinal biopsies from 18 members of a family with Lynch Syndrome II used immunocytochemical studies to characterise immune populations. The findings suggested polyclonal B-cell activation related to T-helper distribution, but the report stated it provided no specific information on management of patients with Lynch syndrome.
A 2024 case report described a female with early presentation of Lynch syndrome and colorectal cancer who, on her third malignant presentation, was re-diagnosed with constitutional mismatch repair deficiency. The report noted an estimated 153,020 cases of colorectal cancer per year, with an increase in diagnoses in younger patients, but provided no trial data or survival numbers.
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.
Cancer Management and Research · 2019 · 26 citations · open access
<p>Novel variants of unknown significance in the <em>PMS2</em> gene identified in patients with hereditary colon cancer</p>
AbstractBackground: Lynch syndrome is associated with genetic variants in mismatch repair ( MMR ) genes. Pathogenic variants in the MLH1 and MSH2 genes occur in most families in which the phenotype is highly penetrant. These testing criteria are likely to miss individuals with Lynch syndrome due to the less penetrant MMR genes, such as MSH6, MLH3, MSH3, and PMS2 . So far, several mutations in the PMS2 gene have been described as responsible for the clinical manifestation of Lynch syndrome. Recent data have reported that families with atypical Lynch phenotype were found to have primarily monoallelic mutations in the PMS2 gene. Methods: We analyzed the PMS2 gene to detect mutations in members of 64 Lynch syndrome families by direct sequencing. Results: We report the identification of several genetic variants in patients with LS, of which three are novel variants. The carriers of these novel variants were also carried of other variants in PMS2 gene and/or in other MMR genes. Conclusion: Therefore, we think that these novel PMS2 variants may act in additive manner to manifestation LS phenotype. Keywords: Lynch syndrome, PMS2 gene, MMR genes, PMS2 variants, synergist effect of MMR variants
American Society of Clinical Oncology Educational Book · 2014 · 3 citations · open access
Lynch Syndrome 101 (Years, That Is)
AbstractLynch syndrome was described over a century ago but information on the medical consequences and optimal management of this disorder continue to amass and evolve. This brief overview highlights the gene-specific and site-specific cancer penetrance and management options for those with Lynch syndrome.
The International Journal of Biological Markers · 1986 · 1 citations
Lymphocyte Subpopulations in Lynch Syndrome Ii: An Immunocytochemical Study on Gastrointestinal Biopsies. Preliminary Report
AbstractGastrointestinal biopsies from 18 members of a family with Lynch Syndrome II were evaluated and immunocytochemical studies were made to characterize the phenotypic expression of the tissue's immune populations. The intestinal findings suggest polyclonal B-cell activation related to the T-helper distribution. Our evaluation provides no specific information so far on the management of patients with Lynch Syndrome II.
Clinical Journal of Gastroenterology · 2024 · 0 citations · open access
Constitutional mismatch repair deficiency: a case on a commonly misinterpreted mutation in colon cancer
AbstractIt is estimated that 153,020 cases of CRC per year, with an increase in diagnoses in younger patients. We present a case of a female with an early presentation of Lynch Syndrome and CRC, who, on her third malignant presentation, was re-diagnosed as a constitutional mismatch repair deficiency.
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.
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