DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for colon adenocarcinoma — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleColon adenocarcinoma maps to a 46-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 adenocarcinoma 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
fibroblast growth factor receptor 4 (FGFR4) — FGFR4 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 1~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8KH8 · 1.49 Å · ligand 1-[4-[(1~{R})-1-[3,5-bis(chloranyl)pyridin-4-yl]ethoxy]-5-cyano-pyridin-2-yl]-3-[6-methanoyl-5-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3-(2-morpholin-4-ylethoxy)pyridin-2-yl]urea (VVW). Experimental structure, not a prediction.
What the evidence adds up to
The 1996 experimental work using an inducible expression system showed that restoring APC in human colorectal cancer cells carrying inactive APC alleles substantially reduced cell growth, and that this reduction was due to apoptosis. The authors concluded that apoptosis operates at the earliest stages of neoplasia, not only in advanced tumours. A separate 1996 review summarised the then-current genetics: the adenoma-carcinoma sequence, the genes for familial adenomatous polyposis and hereditary nonpolyposis coli, and the possibility of molecular diagnosis of syndromic colon cancer. A 2013 review restated four tenets: clonal growth advantage from genetic and epigenetic alterations, multi-step progression, loss of genomic stability, and germline forms of key defects underlying hereditary syndromes.
Clinical management of obstructing colonic cancer is the only area with patient-level data here. A 2019 case report describes a 72-year-old man with descending colon obstruction from adenocarcinoma, treated with a self-expandable metal stent, then two courses of modified FOLFOX6 chemotherapy, followed by left hemi-colectomy without stoma. CT at 14 days after stenting showed significant bowel swelling; after chemotherapy the swelling improved. The patient was disease-free at 6 months after surgery. This is a single case, not a trial. A 2022 French overview states that the priority in obstructed colon cancer is urgent relief of obstruction without compromising oncological outcomes, with low ostomy rates, and that staged procedures can offer outcomes similar to elective surgery, with treatment tailored to patient condition, oncological situation, and surgical expertise. A 2008 Chinese review notes that combined therapy based on radical surgery has improved survival, but a large percentage of patients still die of recurrence and metastasis; newer targeted and chemotherapeutic drugs have improved efficacy, but choosing and combining them rationally remains a challenge. Another 2008 review mentions gene therapy for colon cancer as being in clinical testing, with safety still a hot topic.
No abstract here reports a randomised trial, a survival curve, a response rate, or a comparative efficacy result for any drug in colon adenocarcinoma. The only concrete outcome is the single patient disease-free at 6 months. The molecular reviews are descriptive, not therapeutic. What is missing is precisely what would be needed to repurpose any agent: prospective data with adequate sample sizes, defined patient stratification by molecular subtype or APC status, and trial designs that measure survival or recurrence rather than case reports or mechanistic speculation.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Proceedings of the National Academy of Sciences · 1996 · 492 citations · open access
Apoptosis and APC in colorectal tumorigenesis.
AbstractTumors result from disruptions in the homeostatic mechanisms that regulate cell birth and cell death. In colon cancer, one of the earliest manifestation of this imbalance is the formation of polyps, caused by somatic and inherited mutations of the adenomatous polyposis coli (APC) tumor suppressor gene in both humans and mice. While the importance of APC in tumorigenesis is well documented, how it functions to prevent tumors remains a mystery. Using a novel inducible expression system, we show that expression of APC in human colorectal cancer cells containing endogenous inactive APC alleles results in a substantial diminution of cell growth. Further evaluation demonstrated that this was due to the induction of cell death through apoptosis. These results suggest that apoptosis plays a role not only in advanced tumors but also at the very earliest stages of neoplasia.
American Journal of Molecular Biology · 2013 · 49 citations · open access
Molecular biology of colorectal cancer: Review of the literature
AbstractColorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic epithelium to colon adenocarcinoma. From the analysis of the molecular genesis of colon cancer, four central tenets concerning the pathogenesis of cancer have been established. The first is that the genetic and epigenetic alterations that underlie colon cancer formation promote the cancer formation process because they provide a clonal growth advantage to the cells that acquire them. The second tenet is that cancer emerges via a multi-step progression at both the molecular and the morphologic level. The third is that loss of genomic stability is a key molecular step in cancer formation. The fourth is that hereditary cancer syndromes frequently correspond to germ line forms of key genetic defects whose somatic occurrences drive the emergence of sporadic colon cancers.
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.
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.
Cancer colique en occlusion : quelle prise en charge en 2022 ?
AbstractThe key priority for obstructed colon cancer (OCC) is urgent resolution of the large bowel obstruction with ideally no compromise of oncological outcomes and low initial and permanent ostomy rates. Proactive management is pivotal to decrease the risk of perforation and septic shock. Staged procedures have an important place to provide optimal treatment and offer similar treatment and outcomes as in the elective setting. The approach is tailored to the patient's condition, the oncological situation and expertise of the available surgical team. This overview concludes by proposing a comprehensive treatment algorithm for individualized treatment of OCC.
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.
Progress in the studies of colon cancer recurrence
AbstractColon cancer is one of the most common cancers in China, with an increasing incidence these years. Currently, the combined therapy based on radical surgery has dramatically improved the survival rate and life quality of patients, however, a large percentage of patients still died of recurrence and metastasis. In recent years, the treatment strategies for the recurrence of colon cancer have been greatly advanced, especially the new targeted drugs and chemotherapeutic drugs, which lead to a significantly improved therapeutic efficacy and a better life quality. Therefore, how to choose and use these new treatments synthetically and reasonably become a great challenge to all surgeons, especially to digestive surgeons.
Key words:
Colon cancer; Recurrence
AbstractSurgical treatment of colon cancer is the first choice in the therapy stages,supplemented with systemicor local radiotherapy and chemotherapy.With the developement of molecular biology,there has been a variety of treatment program,some of these methods have been accepted in clinical testing stage.But the safety of the treatment on colon cancer is still a hot topic.
Key words:
colon cancer; cene therapy; safety
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.
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.
