DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for small intestinal adenocarcinoma — screening already-approved drugs against its 48-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSmall intestinal adenocarcinoma maps to a 48-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
approvedSunitinibApproved drugapprovedRegorafenibApproved drug
Structures already discussed alongside small intestinal adenocarcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 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 b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
A retrospective cohort study using the linked Surveillance, Epidemiology, and End Results and Medicare database identified 2123 patients with small-bowel adenocarcinoma and 248,862 patients with colon cancer from 1992 to 2010. Five-year overall survival for small-bowel adenocarcinoma was 34.9% compared to 51.5% for colon cancer. 73.0% of small-bowel patients underwent surgery, and 21.3% received chemotherapy. In contrast to colon cancer, chemotherapy did not improve overall or cancer-specific survival for small-bowel adenocarcinoma regardless of stage; the hazard ratio for chemotherapy compared to surgery alone was 1.04 (95% CI, 0.90-1.22). Only surgery improved survival. The authors concluded that current chemotherapy regimens may be overused and need more rigorous study.
A 2011 review states that aggressive surgical resection provides the best chance of cure, but that despite apparent curative resection the long-term outlook remains poor. That same review claims a survival benefit in advanced disease with oxaliplatin and 5-fluorouracil, but notes the role of adjuvant chemotherapy is not well defined due to the rarity of the disease and lack of randomised controlled trials. A 2019 review notes that small bowel adenocarcinoma has been treated similarly to colorectal cancer in the advanced setting, but that patient outcomes are inferior at all stages and recent molecular studies highlight genomic differences that suggest new future pathways for treatment distinct from colorectal cancer.
One abstract discusses small-molecule drugs for gastrointestinal cancers generally, but does not provide data specific to small intestinal adenocarcinoma. Another abstract concerns recurrent gastrointestinal stromal tumours (GIST) of the small bowel, which is a different histology from adenocarcinoma, and describes tyrosine kinase inhibitor therapy for GIST; this is not applicable to adenocarcinoma.
What is still missing are prospective randomised controlled trials large enough to test adjuvant and palliative chemotherapy regimens specifically for small bowel adenocarcinoma. The retrospective data show no benefit from current chemotherapy, but the sample sizes are small and the regimens are borrowed from colon cancer without validation. Patient stratification by molecular subtype, which the 2019 review suggests may be distinct from colorectal cancer, has not been translated into a completed trial. Funding for multi-centre, histology-specific trials remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Diseases of the Colon & Rectum · 2016 · 84 citations
Treatment and Survival of Small-bowel Adenocarcinoma in the United States
AbstractBACKGROUND: Small-bowel adenocarcinoma is rare and fatal. Because of data paucity, there is a tendency to extrapolate treatment from colon cancer, particularly in the adjuvant stetting. OBJECTIVE: The purpose of this study was to evaluate the current surgical and adjuvant treatments of small-bowel adenocarcinoma and compare with colon cancer. DESIGN: This was a retrospective cohort study. SETTINGS: The linked Surveillance, Epidemiology, and End Results and Medicare database was used at a tertiary referral hospital. PATIENTS: Patients with small-bowel adenocarcinoma and colon cancer identified from 1992 to 2010, using International Classification of Diseases for Oncology, 3 Revision, site, behavior, and histology codes were included. MAIN OUTCOME MEASURES: Overall survival and cancer-specific survival were estimated using the Kaplan-Meier method and competing risk analysis. RESULTS: A total of 2123 patients with small-bowel adenocarcinoma and 248,862 patients with colon cancer were identified. Five-year overall survival rates for patients with small-bowel adenocarcinoma and colon cancer were 34.9% and 51.5% (p < 0.0001). A total of 1550 patients with small-bowel adenocarcinoma (73.0%) underwent surgery, compared with 177,017 patients with colon cancer (71.1%). The proportion of patients who received chemotherapy was similar, at 21.3% for small bowel and 20.0% for colon. In contrast to colon cancer, chemotherapy did not improve overall or cancer-specific survival for patients with small-bowel adenocarcinoma, regardless of stage. Predictors of poor survival for small-bowel adenocarcinoma on multivariate analysis included advanced age, black race, advanced stage, poor tumor differentiation, high comorbidity index, and distal location. Chemotherapy did not confer additional survival benefit compared with surgery alone (HR, 1.04 (95% CI, 0.90-1.22)). LIMITATIONS: This was a retrospective review. The reliance on Medicare data limited granularity and may have affected the generalizability of the results. CONCLUSIONS: The prognosis for small-bowel adenocarcinoma is worse than that for colon cancer, and only surgery improves survival. In contrast to colon cancer, a survival benefit from current chemotherapy regimens for small-bowel adenocarcinoma is not seen, suggesting that it may be overused and needs more rigorous study.
Journal of the National Comprehensive Cancer Network · 2019 · 72 citations · open access
Small Bowel Adenocarcinoma: Etiology, Presentation, and Molecular Alterations
AbstractSmall bowel adenocarcinoma (SBA) is a rare cancer that has been treated similarly to colorectal cancer (CRC) in the advanced setting. Incidence has been increasing as detection efforts have been improving for these challenging-to-diagnose tumors, but patients frequently experience prolonged nonspecific symptoms due to delayed diagnosis. As a result of such delays and likely due to variant biology, patient outcomes for SBA are inferior to those for CRC at all stages of diagnosis. Recent molecular studies highlight the genomic differences underpinning these tumors and suggest new future pathways for treatment, distinct from CRC.
Nacidos del reconocimiento. El reconocimiento como un elemento humanizador fundamental.
AbstractGastrointestinal (GI) cancers encompass a group of malignancies affecting the digestive system, including the stomach, esophagus, liver, colon, rectum and pancreas. These cancers represent a significant global health burden, necessitating effective treatment strategies. Small-molecule drugs have emerged as crucial therapeutic options in the fight against GI cancers due to their oral bioavailability, targeted mechanisms of action, and well-established safety profiles. The review then elucidates the clinical applications and synthetic methods of clinically approved small-molecule drugs for the treatment of GI cancer, shedding light on their mechanisms of action and their potential in mitigating GI cancer progression. The review also discusses future prospects and the evolving landscape of small-molecule drug development in GI oncology, highlighting the potential for personalized medicine. In summary, this review provides valuable insights into cutting-edge strategies for harnessing clinically approved small-molecule drugs to combat GI cancer effectively.
Malignant tumours · 2018 · 0 citations · open access
Multidisciplinary approach in treatment of recurrent gastrointestinal stromal tumors: a case report and literature review
AbstractCurrently, the standard treatment of recurrent gastrointestinal stromal tumors (GIST) is life-long targeted therapy with tyrosine kinase inhibitors. Imatinib is administered as a first-line therapy. Due to the high mutational potential of tumor cells the secondary drug resistance develops in an overwhelming number of patients, which leads to the necessity of switching to second (sunitinib) and third (regorafenib) line therapy. In addition, the role of the surgical method in the complex treatment of advanced GIST has recently been updated. This article gives an example of long-term follow-up and treatment of a patient with recurrent small bowel GIST. The effectiveness of the combined approach in the treatment of this complex category of patients has been demonstrated.
Breeding better maize germplasm for drier and hotter production environments
AbstractAdenocarcinoma of the small intestine is rare in comparison with other gastrointestinal malignancies but its incidence is rising. It often presents at an advanced stage due to the non-specific symptomatology. More recent advances in small intestinal visualisation including video capsule endoscopy and double balloon enteroscopy may facilitate diagnosis in patients with suspected small intestinal neoplasia. At present aggressive surgical resection provides the best chance of cure of small intestinal adenocarcinoma. Despite apparent curative resection the long-term outlook remains poor. The role of adjuvant chemotherapy is not well defined due to the rarity of the disease and lack of randomised controlled trials; however, there appears to be a survival benefit in advanced disease with the use of oxaliplatin and 5-fluorouracil. We reviewed the clinical aspects of this aggressive condition focusing on the pathological associations, available diagnostic modalities and current management options. Three cases are included to illustrate the review.
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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