DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for gastrointestinal stromal tumor — 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 moduleGastrointestinal stromal tumor 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
approvedSunitinibApproved drugapprovedRegorafenibApproved drug
Structures already discussed alongside gastrointestinal stromal tumor 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
Gastrointestinal stromal tumours are rare mesenchymal tumours of the digestive tract. Their true incidence has been difficult to establish because of past diagnostic difficulties and their rarity. Before the introduction of molecular-targeted therapy, prognosis was extremely poor and there was very little to offer patients in the way of treatment.
The targeted tyrosine kinase inhibitor imatinib mesylate has been shown in phase III trials to be a dramatically effective agent, but the duration of its benefits is finite and drug resistance is an increasingly common phenomenon. A second targeted tyrosine kinase inhibitor, sunitinib malate, was approved for imatinib-resistant gastrointestinal stromal tumours after encouraging results. Despite these advances, the surgeon still plays a pivotal role in the management of primary tumours and even in the metastatic setting.
The success with imatinib and sunitinib has encouraged investigators to reevaluate the role of surgery in advanced disease. Adjuvant and neoadjuvant trials of imatinib were underway as of 2007. The multidisciplinary management of gastrointestinal stromal tumours serves as a model for combining targeted molecular therapies with traditional treatment modalities to improve survival in advanced malignancies.
What is still missing are mature data from ongoing adjuvant and neoadjuvant trials, strategies to overcome acquired resistance to imatinib, and further molecular-targeted therapies beyond the two approved agents. The rarity of the disease continues to make large-scale randomised trials difficult to fund and complete, and patient stratification based on molecular biology remains a work in progress rather than a settled clinical tool.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Gastroenterology · 2007 · 57 citations
Current issues in gastrointestinal stromal tumors: incidence, molecular biology, and contemporary treatment of localized and advanced disease
AbstractPURPOSE OF REVIEW: Few areas in oncology have witnessed the major paradigm shift that has been noted in the understanding and management of gastrointestinal stromal tumors. This review highlights the progress made over the last 2 years. RECENT FINDINGS: Population-based studies have provided insight into the true incidence of gastrointestinal stromal tumors. Improved understanding of the molecular biology has provided prognostic implications and may guide treatment in the future. More mature follow-up data from phase III trials have proven that the targeted tyrosine kinase inhibitor imatinib mesylate is a dramatically effective agent, but the duration of its benefits are finite, and drug resistance is an increasingly more common phenomenon. Adjuvant and neoadjuvant trials of imatinib are currently underway. A second targeted tyrosine kinase inhibitor, sunitinib malate, has been approved for the treatment of imatinib-resistant gastrointestinal stromal tumors after recent encouraging results. Finally, the success with imatinib and sunitinib has encouraged investigators to reevaluate the role of surgery in advanced gastrointestinal stromal tumors. SUMMARY: The multidisciplinary management of gastrointestinal stromal tumors serves as a model of how new targeted molecular therapies can be combined with traditional treatment modalities to improve survival in advanced malignancies.
Japanese Journal of Clinical Oncology · 2010 · 16 citations · open access
Clinical Efficacy and Safety of Sunitinib After Imatinib Failure in Japanese Patients with Gastrointestinal Stromal Tumor
AbstractBACKGROUND: Imatinib used to be the only effective treatment for advanced gastrointestinal stromal tumor. However, early clinical reports have shown that sunitinib has substantial anticancer activity in patients with advanced gastrointestinal stromal tumor after failure of imatinib. METHODS: Eighteen Japanese patients with advanced gastrointestinal stromal tumor who were resistant or intolerant to previous treatment with imatinib were entered into this study. These patients were given sunitinib orally, once daily at a 50-mg starting dose, in 6-week cycles with 4 weeks on and 2 weeks off treatment. Tumor response and drug safety were then evaluated. RESULTS: Median time-to-treatment failure was 207 days. Overall, 5.6% (1/18) of patients achieved partial response, 38.9% (7/18) had stable disease and 44.4% (8/18) had progressive disease. The common adverse events were hand-foot syndrome, liver dysfunction, fatigue, anorexia and hypertension. Mild anemia, leukocytopenia and neutropenia were also noted. Nine patients required dose reduction or cessation because of adverse events. CONCLUSIONS: This study demonstrates that sunitinib may be an effective agent for advanced gastrointestinal stromal tumor after failure of imatinib in clinical practice.
Cambridge University Press eBooks · 2008 · 11 citations
Gastrointestinal stromal tumours
AbstractGastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours that can occur anywhere in the gastrointestinal tract. GISTs have been difficult to diagnose in the past which, along with their rarity, makes their incidence hard to estimate. In the past, there was also very little to offer GIST patients in the way of treatment, and the prognosis was extremely poor. However, recent understanding of the molecular pathology involved in GISTs has made diagnosis more accurate and effective treatments are now available with molecular-targeted therapy. As research continues, it is likely that more molecular-targeted therapies will become available for this condition.
AbstractGastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the GI tract and constitute less than 1% of all digestive tract tumors--the stomach is the most common site. Regorafenib is a multi-tyrosine kinase inhibitor with regulatory approvals granted for colorectal cancers and GIST. The US FDA granted approval for the use of regorafenib in February 2013 in patients with advanced GIST for those who had failed on imatinib and sunitinib. This was based on a pivotal Phase III double-blind placebo controlled randomized trial that showed that there was a significant improvement in progression-free survival for patients on regorafenib.
Revista do Colégio Brasileiro de Cirurgiões · 2009 · 6 citations · open access
O papel atual do cirurgião no tratamento do GIST
AbstractRecent progress in gastrointestinal stromal tumor's (GIST) treatment were responsible for changing GIST's natural history. Knowledge acquirement of molecular mechanism-based systemic therapy gave rise to the development of targeted antineoplastic drugs capable of reaching outcomes that had never been reached before. The introduction of imatinib in the clinical practice not only changed GIST's patients survival but also shifted paradigms. However, besides all these new advances and the improved results with imatinib, the surgeon still plays a pivotal role in the management of the primary GIST tumor and even in the metastatic setting.
Serving the Homeless through Recreation Programs. Research Update.
AbstractOptimal treatment for patients suffering from gastrointestinal stromal tumors (GIST) is based on an interdisciplinary treatment approach. Austrian representatives of Medical and Surgical Oncology, Pathology, Radiology, Nuclear Medicine, Gastroenterology, and Laboratory Medicine issued this manuscript on a consensual base within the context of currently available and published literature. This paper contains guidelines and recommendations for diagnosis, therapy, and follow-up of GIST patients in Austria.
Reviews on Recent Clinical Trials · 2007 · 3 citations
Critical Update and Emerging Trends in Imatinib Treatment for Gastrointestinal Stromal Tumor
AbstractThe extraordinary success of imatinib in gastrointestinal stromal tumor (GIST) represents a model for molecularly targeted therapy of solid tumors. Research is currently going to identify the molecular basis of mechanisms of action and drug resistance. For the optimal management of the patients treated, a multidisciplinary approach, including medical oncologists, surgeons, pathologists, and radiologists is needed. In this article, we reviewed recent advances in the clinical management of GIST patients treated with imatinib, and in the knowledge of the molecular mechanisms that are basic to imatinib effects.
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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