DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for colon carcinoma in situ — screening already-approved drugs against its 31-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleColon carcinoma in situ maps to a 31-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
approvedRegorafenibApproved drugapprovedRuxolitinibApproved drug
Structures already discussed alongside colon carcinoma in situ in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Human JAK2 JH1 domain — Ruxolitinib has a real, experimentally solved structure in complex with this target (PDB 6WTN, 1.83 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet rxtdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6WTN · 1.83 Å · ligand Ruxolitinib (RXT). Experimental structure, not a prediction.
What the evidence adds up to
A 2018 phase two randomised double-blind study tested ruxolitinib plus regorafenib against placebo plus regorafenib in 396 patients with relapsed or refractory metastatic colorectal cancer. The trial was terminated early: the high-inflammation substudy (C-reactive protein >10 mg/L, n=175) was stopped for futility at interim analysis, and the low-inflammation substudy (n=221) was stopped by sponsor decision. Overall survival showed no significant difference in either group (high-inflammation hazard ratio 1.040, 95% CI 0.725–1.492; low-inflammation hazard ratio 0.767, 95% CI 0.478–1.231). Progression-free survival was similarly unchanged. Anaemia was the most common haematologic adverse event; no new safety signals emerged. The authors concluded that adding ruxolitinib to regorafenib did not improve survival.
Earlier literature on colon carcinoma in situ is sparse and entirely descriptive. A 1970 report described a single case of multicentric nonpolypoid carcinoma in situ of the colon, a lesion the authors said had not previously been described in that location. They considered the lesions potentially malignant but probably benign at excision, and recommended local resection with a careful search for additional bowel tumours. A 1973 case series from Massachusetts General Hospital reported nine patients in whom an abdominal wall abscess was the presenting sign of colon carcinoma invading the abdominal wall; the authors noted such patients are potentially curable. A 1986 five-year follow-up of 224 resectable colon carcinomas found a 43% five-year survival rate, with only 23% of tumours classified as early by histology; the authors stated that active surveillance of conventional high-risk groups would not significantly improve overall statistics. A 1995 multicentre trial randomised 929 patients with stage III colon cancer to adjuvant therapy regimens, but the abstract gives no results. A 1996 review summarised genetic advances in the adenoma-carcinoma sequence and the identification of genes for familial adenomatous polyposis and hereditary nonpolyposis coli, noting that molecular diagnosis of syndromic colon cancer was then possible.
What is missing for carcinoma in situ of the colon is any modern prospective trial. No drug has been tested specifically for this stage. The only randomised drug study available concerns metastatic disease and produced negative results. No data exist on whether JAK inhibition or any other targeted therapy alters the natural history of non-invasive lesions. A trial would require a reliable biomarker to distinguish lesions that will progress from those that will not, and a population willing to undergo serial colonoscopic surveillance with biopsy. Funding for such a study is absent, and no pharmaceutical company has shown interest in a condition that is usually managed by local excision alone.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer Medicine · 2018 · 48 citations · open access
Randomized, double‐blind, phase two study of ruxolitinib plus regorafenib in patients with relapsed/refractory metastatic colorectal cancer
AbstractBACKGROUND: The Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway plays a key role in the systemic inflammatory response in many cancers, including colorectal cancer (CRC). This study evaluated the addition of ruxolitinib, a potent JAK1/2 inhibitor, to regorafenib in patients with relapsed/refractory metastatic CRC. METHODS: In this two-part, multicenter, phase 2 study, eligible adult patients had metastatic adenocarcinoma of the colon or rectum; an Eastern Cooperative Oncology Group performance status of 0-2; received fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy (if no contraindication); and if KRAS wild-type (and no contraindication), an anti-epidermal growth factor receptor therapy; and progressed following the last administration of approved therapy. Patients who received previous treatment with regorafenib, had an established cardiac or gastrointestinal disease, or had an active infection requiring treatment were excluded. The study was conducted in 95 sites in North America, European Union, Asia Pacific, and Israel. After an open-label, safety run-in phase (part 1; ruxolitinib 20 mg twice daily [BID] plus regorafenib 160 mg once daily [QD]), the double-blind, randomized phase (part 2) was conducted wherein patients were randomized 1:1 to receive ruxolitinib 15 mg BID plus regorafenib 160 mg QD [ruxolitinib group] or placebo plus regorafenib 160 mg QD [placebo group]. Part 2 included substudy 1 (patients with high systemic inflammation, ie, C-reactive protein [CRP] >10 mg/L) and substudy 2 (patients with low systemic inflammation, ie, CRP ≤10 mg/L); the primary endpoint was overall survival (OS). RESULTS: The study was terminated early; substudy 1 was terminated for futility at interim analysis and substudy 2 was terminated per sponsor decision. Ruxolitinib 20 mg BID was well tolerated in the safety run-in (n = 11). Overall, 396 patients were randomized (substudy 1: n = 175 [ruxolitinib group, n = 87; placebo group, n = 88]; substudy 2: n = 221 [ruxolitinib group, n = 110; placebo group, n = 111]). There was no significant difference in OS or progression-free survival (PFS) between treatments in substudy 1 (OS: hazard ratio [HR] = 1.040 [95% confidence interval: 0.725-1.492]; PFS: HR = 1.004 [0.724-1.391]) and substudy 2 (OS: HR = 0.767 [0.478-1.231]; PFS: HR = 0.787 [0.576-1.074]). The most common hematologic adverse event was anemia. No new safety signals with ruxolitinib were identified. CONCLUSIONS: Although addition of ruxolitinib to regorafenib did not show increased safety concerns in patients with relapsed/refractory metastatic CRC, this combination did not improve OS/PFS vs. regorafenib plus placebo.
Abscess of the abdominal wall as the presenting sign in carcinoma of the colon
AbstractInvasion of the abdominal wall by carcinoma of the colon may produce an abscess of the abdominal wall. On rare occasions this may be the presenting sign. Nine such cases that were treated at Massachusetts General Hospital are reported here, and representative case histories are summarized for four of them. Our purpose is to draw attention to this rare occurrence and to indicate that such patients are potentially curable.
Diseases of the Colon & Rectum · 1970 · 13 citations
Carcinoma in situ of the colon
AbstractSummary A case of multicentric neoplasia of the colon is described. At least two of the lesions fit all the criteria for nonpolypoid carcinoma in situ, a lesion previously not described in that location. The lesions are believed to have been potentially malignant, but at the time of excision probably were benign. The incidental discovery of nonpolypoid carcinoma in situ of the colon should be an indication for local resection and careful search for additional bowel tumors.
Resectable Colonic Carcinoma—A Five Year Experience
AbstractClinical characteristics, mode of presentation and pathological features of resectable carcinoma of the colon have been studied in 224 cases presenting between January 1971 and December 1975. Minimum length of follow-up is five years and is complete. Forty-three per cent of patients survived five years or more, only 23 per cent of tumours being early in histological terms. The conventional high risk groups contributed little to the total and their active surveillance will not significantly improve the overall statistics.
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.
AbstractMost patients with colon carcinoma present with resectable disease in which any residual tumor is microscopic. This multicenter trial evaluated the efficacy of two adjuvant regimens for improving surgical cure rates in patients with stage III colon cancer. Researchers randomized 929 patients …
Congenital absence of part of the colon associated with carcinoma of the colon
AbstractJournal Article Congenital absence of part of the colon associated with carcinoma of the colon Get access Kenneth M Douglas Kenneth M Douglas Surgical Registrar Glasgow Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 41, Issue 168, January 1954, Pages 373–375, https://doi.org/10.1002/bjs.18004116810 Published: 06 December 2005
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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