DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for colon adenoma — screening already-approved drugs against its 26-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleColon adenoma maps to a 26-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 colon adenoma 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
The abstracts describe the biology of colorectal adenomas and one clinical trial of a drug, sulindac, in sporadic colorectal adenomas. The genetic background is well established: mutations in the adenomatous polyposis coli (APC) gene are found in 85% of adenomas and over 80% of colorectal tumours, and this is an early event in the adenoma-carcinoma sequence. APC function is linked to beta-catenin regulation and chromosome instability, but the exact mechanisms are not fully understood. A 1996 review notes that genetic research had enabled molecular diagnosis of syndromic colon cancer and suggested approaches to gene-based therapies, but no such therapy is described in these abstracts. A 1947 paper states that surgery at that time offered the only hope of cure or palliation for colon cancer, and a 2019 case report describes a single 72-year-old patient with obstructing colonic cancer treated successfully with a self-expandable stent, neoadjuvant mFOLFOX6 chemotherapy, and subsequent left hemi-colectomy; he was disease-free for 6 months after surgery.
The only drug trial reported is a randomised placebo-controlled study of sulindac 400 mg daily for 4 months in 36 patients with sporadic colorectal adenomas, of whom 32 completed the trial (16 per group). In the sulindac group, the average diameter of 59 adenomas decreased from 3.6 ± 2.2 mm before treatment to 2.4 ± 1.5 mm after treatment (P < 0.001), and the degree of atypia also decreased significantly. In the control group, average diameters were 4.6 ± 2.5 mm before and 3.7 ± 2.2 mm after treatment, with no significant difference and no change in morphology or atypia. No severe side-effects of sulindac were reported. The authors conclude that sulindac is effective in reducing the size and degree of atypia of sporadic colorectal adenomas, but they explicitly state that its long-term effect remains to be tested.
The evidence base is therefore narrow. The sulindac trial is small, short-term, and does not report on adenoma recurrence or prevention of progression to carcinoma. No data are provided on whether the observed regression translates into reduced cancer incidence. The other abstracts contribute no therapeutic data for adenomas: they cover genetic mechanisms, pathogenesis in familial polyposis, and a single case of obstructing cancer treatment. What is still missing is a larger, longer randomised trial of sulindac or related agents in sporadic adenomas, with follow-up long enough to assess recurrence rates and cancer outcomes, and stratification by APC mutation status or other genetic markers, since the abstracts suggest these may influence response.
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 · 2000 · 23 citations · open access
Catenins and their associated proteins in colorectal cancer.
AbstractColorectal cancer is the second most common cause of cancer mortality in the western world. Colorectal cancer has been well studied, and the genetic steps involved in the adenoma to carcinoma sequence have been well elucidated. The first genetic alteration, found in 85% of adenomas, are mutations in the adenomatous polyposis coli (APC) gene. However, the consequences of this and the exact function of APC in the colon is not fully understood. It has been suggested that APC could function through its regulation of beta-catenin, an ubiquitous cytoskeletal protein with multiple binding specificities resulting in diverse functions including cell growth, adhesion, and migration. Any change in these associations may play a role in colorectal cancer development and progression.
AbstractCarcinoma is by long odds the most commonly observed tumor of the colon and accounts for about 7 per cent of all cancer. Because of years of intensive study and in spite of inherent difficulties of surgical attack, there has been a pronounced betterment of diagnosis and a remarkable improvement in the results of treatment of this disease. Although the management of cancer of the colon may be considered satisfactory or even good when compared to that of cancer in other parts of the alimentary tract, it is still capable of great improvement by intensifying the application of present known methods of diagnosis and treatment. Surgery, which at present offers the only hope of cure or palliation, has advanced to a point where the reduction of mortality and morbidity and the good end results of treatment of the disease in its early stages reach far beyond the skill of diagnosis.
Diseases of the Colon & Rectum · 1983 · 14 citations
Pathogenesis of polyps (adenomas)
AbstractThe pathogenesis of adenomas in adenomatous polyposis of the gastrointestinal tract (familial polyposis coli, FPC) is not completely known. The morphologic features of the dysplastic epithelium and the morphogenesis of adenomas in FPC have been well described. Studies of the precursors to adenomatous epithelium have identified histopathologic, ultrastructural, and epithelial proliferative abnormalities in grossly normal colonic mucosa of FPC patients. The role of the intraluminal environment and the mechanisms of its interaction with the mucosa appear to be important areas for research directed at the pathogenesis of adenomas in FPC, due to the implications for therapy.
World Journal of Clinical Cases · 2019 · 10 citations · open access
Successful treatment of obstructing colonic cancer by combining self-expandable stent and neoadjuvant chemotherapy: A case report
AbstractBACKGROUND: Surgery 5-10 d after stent insertion was recommended by the European Society of Gastrointestinal Endoscopy for obstructing colonic cancer. For some obstructive patients, this may be not a good choice. Here, we report the successful treatment of obstructing colonic cancer by combining self-expandable stent and neoadjuvant chemotherapy. CASE SUMMARY: The patient was a 72-year-old man who was admitted with a chief complaint of abdominal pain for more than 1 mo. Computed tomography (CT) scanning revealed that there was a mass in the descending colon, which led to intestinal obstruction. On admission, a series of therapeutic measures, such as fasting and water deprivation, gastrointestinal decompression, total parenteral nutrition, and octreotide acetate, were taken to improve the obstructive symptoms. At the same time, a self-expandable metal stent was successfully placed across the stenosis, and a biopsy was obtained and diagnosed as adenocarcinoma. CT scanning 14 d after insertion of the stent revealed that the intestine was swollen significantly. Systemic chemotherapy with modified FOLFOX6 (mFOLFOX6) was administered. After two courses of mFOLFOX6, CT scanning showed clearly that swelling of the intestine was improved. Subsequently, the patient underwent left hemi-colectomy without stoma placement. The postoperative course was uneventful, and he has been disease-free for 6 mo after surgery. CONCLUSION: This modified treatment strategy may provide an alternative therapy for patients with obstructing colonic cancers.
Revista Española de Enfermedades Digestivas · 2005 · 8 citations · open access
APC and chromosome instability in colorectal cancer
AbstractColon cancer is a common disease that can be sporadic or familial. An inactivated adenomatous polyposis coli (APC) suppressor gene is found in over 80% of colorectal tumors, this being an early alteration in the development of adenomatous polyps. APC function is not only critical for tumor initiation and progression, and chromosome instability (CIN) is another characteristic dependent at least partly on APC mutations.
Current Opinion in Gastroenterology · 1996 · 3 citations
The genetics of colorectal cancer
AbstractThis article reviews the past year's advances concerning the genetics of colon cancer. Previous to this year, the genetic events involved in the adenoma-carcinoma sequence were characterized and the genes responsible for familial adenomatous polyposis and hereditary nonpolyposis coli syndromes identified. Genetic research has made possible the molecular diagnosis of syndromic colon cancer, provided clues to the cellular mechanisms of cancer pathogenesis, and suggested approaches to novel gene-based therapies. The past year has added to this knowledge base in two major areas: the inherited predisposition or familial risk for colorectal cancer and the molecular biology of colon cancer pathogenesis.
Current Opinion in Gastroenterology · 1996 · 2 citations
The genetics of colorectal cancer
AbstractThis article reviews the past year's advances concerning the genetics of colon cancer. Previous to this year, the genetic events involved in the adenoma-carcinoma sequence were characterized and the genes responsible for familial adenomatous polyposis and hereditary nonpolyposis coli syndromes identified. Genetic research has made possible the molecular diagnosis of syndromic colon cancer, provided clues to the cellular mechanisms of cancer pathogenesis, and suggested approaches to novel gene-based therapies. The past year has added to this knowledge base in two major areas: the inherited predisposition or familial risk for colorectal cancer and the molecular biology of colon cancer pathogenesis.
Chinese Journal of Digestive Diseases · 2002 · 0 citations
Clinical study of sulindac in the treatment of sporadic colorectal adenomas
AbstractOBJECTIVE: To investigate the efficacy of sulindac in the treatment of sporadic colorectal adenomas. METHODS: Thirty‐six patients who were diagnosed colonoscopically and pathologically with sporadic colorectal adenomas were randomly divided into two groups. The sulindac group took 400 mg sulindac daily for 4 months and the patients in the control group were given a placebo treatment for the same period of time. All patients underwent pancolonoscopy at the end of the study. The number, size, morphology, and degree of atypia of the adenomas were compared before and after treatment. RESULTS: Four patients were dropped from the study (three in the sulindac group, one in the control group). Sixteen patients in each group completed the trial. In the sulindac group, the average diameter of 59 adenomas before treatment was 3.6 ± 2.2 mm, which was significantly larger than that after treatment (2.4 ± 1.5 mm; P < 0.001). The morphology of adenomas also changed significantly. The degree of atypia of adenomas also decreased after treatment ( P < 0.001). No severe side‐effects of sulindac were found during the study. In the control group, the average diameters of adenomas before and after treatment were 4.6 ± 2.5 mm and 3.7 ± 2.2 mm, respectively. There was no significant difference between the average diameters of the adenomas before or after treatment ( P > 0.05), nor was there any change in the morphology or the degree of atypia of the adenomas. CONCLUSIONS: Sulindac is effective in reducing the size and degree of atypia of adenomas. This trial demonstrated that sulindac has a regressive effect on sporadic colorectal adenomas. However, its long‐term effect remains to be tested.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
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