DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for gallbladder papillary neoplasm — screening already-approved drugs against its 11-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGallbladder papillary neoplasm maps to a 11-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 gallbladder papillary neoplasm 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
NRAS proto-oncogene, GTPase (NRAS) — NRAS 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZIO · 1.55 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
Of 57 gallbladder cancer specimens examined, 23 were classified as intracholecystic papillary-tubular neoplasm (ICPN) and 34 as non-ICPN. The ICPN group had a 3-year survival rate of 91% compared to 52% for non-ICPN, with lymph node metastases in 6% versus 43% and distant metastases in 0% versus 6%. Mean age was 69 versus 74 years, mean tumour diameter 2.8 versus 2.6 cm, and invasion depth was Tis+T1 in 14 of 23 ICPN cases versus 13 of 34 non-ICPN cases. KRAS gene mutations were found in only 1 of 13 ICPN cases tested. Cell lineage in ICPN was biliary-type in 13 cases, gastric-type in 8, and intestinal-type in 2, a distribution that differs from pancreatic IPMN where gastric and intestinal types are more common.
In a separate series of 1,536 cholecystectomies performed between 1992 and 2001, 14 cases of gallbladder cancer were diagnosed only after surgery, none by intraoperative frozen section. The ratio of men to women was 3 to 11, mean age 69.4 years, clinical symptoms were nonspecific, and mortality was 57%. Gallbladder cancer is described as a rare neoplasm with high mortality and poor prognosis, usually correlated with cholelithiasis, and seldom diagnosed preoperatively due to indolent tumour progression.
A 2021 case report describes an intracholecystic papillary neoplasm with invasive mucinous adenocarcinoma and signet ring cells as a rare, aggressive variety of gallbladder cancer with symptoms mimicking cholecystitis. Survival and prognosis are reported as worse than other types of gallbladder cancer despite surgery and chemotherapy. A 2015 review states that gallbladder cancer prognosis is often dismal due to late diagnosis and lack of effective therapeutic options, with chronic gallstone carriage as the main risk factor leading to a metaplasia–dysplasia–carcinoma sequence. The review identifies inactivation of tumour suppressor pathways as an early carcinogenic event and notes that genome-level alterations such as loss of heterozygosity, microsatellite instability, and epigenetic alterations arise early and increase progressively.
What is still missing are prospective trials that stratify patients by ICPN versus non-ICPN histology, given the large survival difference observed in a single retrospective series of 57 patients. No randomised controlled trials of any drug for gallbladder papillary neoplasm are reported in these abstracts. The molecular subtypes that might guide targeted therapy remain uncharacterised at the level needed for clinical testing, and the funding for such translational work is not described.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Translational Gastroenterology and Hepatology · 2016 · 12 citations · open access
Squamous cell carcinoma of the gallbladder
AbstractGallbladder cancer is the most common malignant tumor of the biliary tract. The majority of cases are adenocarcinoma (AC). Pure squamous cell carcinoma (SCC) of gallbladder accounts only 3% of the malignant neoplasm of this organ. Many patients are at advanced stage when diagnosed and have bad therapeutic efficacy. At present, radical surgery is the only chance to gain long-term survival for patients with early-stage gallbladder cancers. Recent reports have shown a benefit of adjuvant chemoradiation in this type of tumor. At present, no therapy is defined for unresectable cancer of the gallbladder, especially for SCC.
The Showa University Journal of Medical Sciences · 2014 · 11 citations · open access
Clinicopathological Study of Intracholecystic Papillary-Tubular Neoplasms (ICPNs) of the Gallbladder
AbstractIntracholecystic papillary-tubular neoplasm (ICPN) has recently been proposed as a new disease concept in the classification of gallbladder tumors. ICPN is defined as a papillary or polypoid glandular neoplasm forming a localized, non-invasive mass (≥ 1cm) in the gallbladder. We analyzed the clinicopathological characteristics of ICPN. Resected gallbladder cancer specimens from 57 patients were classified as ICPN or non-ICPN and clinicopathological characteristics were compared. ICPN cell characteristics were also analyzed using immunostaining and genetic analysis. Twenty-three cases were classified as ICPN and 34 as non-ICPN. In the ICPN and non-ICPN groups, mean ages were 69 and 74 years, male:female ratios were 14:9 and 15:19, mean tumor diameters were 2.8 and 2.6cm, invasion depths were Tis+T1/T2+T3 in 14/9 cases and 13/21 cases, lymph node metastases were present in 6% and 43%, distant metastases in 0% and 6% and 3-year survival rates were 91% and 52%, respectively. Significant intergroup differences were seen in lymph node metastases and the 3-year survival rate. ICPN cell lineage was biliary-type in 13 cases, gastric-type in 8 and intestinal-type in 2. This proportion differs from that of pancreatic intraductal papillary mucinous neoplasm (IPMN), in which gastric- and intestinal-type are more common. KRAS gene mutations were only seen in 1 of 13 ICPN cases. ICPN is frequently seen in gallbladder cancer, showing similar pathology to pancreatic IPMN, which is considered to have a relatively good prognosis among pancreatic cancers. However, ICPN cell characteristics are not necessarily identical to those of pancreatic IPMN.
World Journal of Gastroenterology · 2013 · 11 citations · open access
Metachronous intracystic and intraductal papillary neoplasms of the biliary tree
AbstractA 77-year-old woman complained of epigastralgia, and a tumor (5 cm in diameter) of the gallbladder neck was detected by image analysis. Following cholecystectomy, the tumor was pathologically diagnosed as intraductal papillary neoplasm (IPN), gastric type, with associated invasive carcinoma. About 10 mo later, intraluminal multiple masses (3 foci, up to 1.8 cm) were noted in the extrahepatic bile duct, and the resected specimen showed that all tumors had similar gross and microscopic features as seen in gallbladder IPN without invasion, and they were synchronous multiple lesions. This case showed a papillary tumor of the gallbladder of gastric phenotype, and confirmed that the gallbladder is a target of IPN in addition to the bile ducts.
Klinicka onkologie · 2013 · 9 citations · open access
Primary Gallbladder Cancer Discovered Postoperatively after Elective and Emergency Cholecystectomy
AbstractBACKGROUND: Gallbladder cancer is a rare neoplasm associated with high mortality and poor prognosis. It is usually correlated with cholelithiasis and presents more commonly in elderly and female patients. Diagnosis is seldom made preoperatively because of the indolent progression of the tumor. METHODS: The hospitalization and surgical records of our surgical department were examined from January 1992 to December 2001, searching for patients who had undergone cholecystectomy. Additionally, the histopathological diagnoses of the same period were studied searching for patients with the diagnosis of gallbladder cancer established post-operatively and not intraoperatively by frozen section. RESULTS: In the period of 1992- 2001, a total of 1,536 cholecystectomies took place and 14 cases of gallbladder cancer were diagnosed postoperatively. The ratio of men to women is 3/ 11 with a mean age of 69.4 years. The clinical symptoms were nonspecific and mortality was 57%. CONCLUSION: In most cases gallbladder cancer is diagnosed after cholecystectomy and even in these cases it can be in an advanced stage and the prognosis of this rare neoplasm is poor.
Encyclopedia of Life Sciences · 2015 · 5 citations
Molecular Genetics of Gallbladder Cancer
AbstractAbstract Gallbladder cancer (GBC) is a deadly biliary neoplasia with marked ethnic and geographical distribution. The prognosis of GBC is often dismal due to late diagnosis and lack of effective therapeutic options. The main risk factor for GBC is gallstone carriage over long periods of time, which leads to persistent damage and chronic inflammation. This condition promotes genetic/epigenetic alterations and the progressive impairment of the epithelial architecture, mainly through a metaplasia–dysplasia–carcinoma sequence. New molecular alterations have been identified that may help improve the clinical management of patients through the application of more specific therapies. The application of new DNA sequencing technologies is making it possible to catalogue the spectrum of genetic alterations that characterise GBC and is aiding in the understanding of the biology behind gallbladder carcinogenesis. Here, a stepwise model of morphogenetic progression from inflammatory to neoplastic tissues is proposed based on currently available evidence. Key Concepts Gallbladder cancer is essentially an inflammatory disease, primarily caused by chronic exposure of the epithelium to gallstones. Morphological alterations of the epithelium arise mainly through a metaplasia–dysplasia–carcinoma sequence. Inactivation of tumour suppressor pathway is an early and important carcinogenic event for gallbladder cancer. Genome‐level alterations such as loss of heterozygosity, microsatellite instability and epigenetic alterations arise early during gallbladder carcinogenesis and increase progressively to advanced stages. Prevention of chronic inflammation may reduce the onset of early genetic alterations and therefore contribute to reducing gallbladder cancer mortality. A future challenge is to elucidate molecular subtypes of GBC and identify new potential therapeutic targets in order to improve patient survival.
Diagnosis and treatment of incidental gallbladder cancer
AbstractUnexpected gallbladder cancer (UGC) is a sort of gallbladder cancer discovered during or after laparoscopic cholecystectomy (LC) which was diagnosed as benign gallbladder disease before surgery. With the high incidence of gallstones in China, the number of patients with UGC increases as well.However, due to the lack of randomized controlled trials on UGC, unified treatment has not been established, and argues on how LC will influence the prognosis of UGC still exist. Surgery for gallbladder cancer is technically challenging. The extent of resection varies based on a number of factors, and controversy exists regarding what constitutes an acceptable resection. We believe that satisfying treatment results are based on the surgical techniques, acute evaluation of different cases and wisely-chosen surgical procedures. This paper summarized therapeutic strategies for UGC based on our clinical experiences.
Key words:
Gallbladder neoplasms, unexpected; Diagnosis; Treatment
Revista Argentina de Cirugía · 2021 · 1 citations · open access
Adenocarcinoma mucinoso de vesícula biliar originado en neoplasia papilar intracolecística
AbstractIntracholecystic papillary neoplasm with invasive mucinous adenocarcinoma and signet ring cells is a rare, aggressive variety of gallbladder cancer, with symptoms mimicking cholecystitis. Survival and prognosis are worse that other types of gallbladder cancer despite surgery and chemotherapy. The aim of this article is to describe a case of a rare gallbladder cancer with specific histology and the treatment performed
68Ga-DOTANOC PET/CT Detects a Rare Case of Metastatic Neuroendocrine Neoplasm of the Gallbladder
AbstractABSTRACT: Gallbladder neuroendocrine neoplasms (NENs) are rare tumors of the biliary system. These neoplasms express somatostatin receptors, and hence radiolabeled somatostatin analog 68Ga-DOTANOC is used as a PET radiotracer in detection and staging. Gallbladder NEN cannot be differentiated from an adenocarcinoma of the gallbladder based on clinical symptoms or routine radiological imaging such as ultrasound or CT. These are either diagnosed postcholecystectomy or after biopsy from primary or metastatic sites. We present a rare case of gallbladder NEN detected on 68Ga-DOTANOC PET/CT.
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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