DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for salivary gland carcinoma — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSalivary gland carcinoma maps to a 45-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 salivary gland carcinoma 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
lysine demethylase 6A (KDM6A) — KDM6A 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 e7zdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6FUL · 1.649 Å · ligand 1-methyl-5-oxidanyl-4-oxidanylidene-pyridine-2-carboxylic acid (E7Z). Experimental structure, not a prediction.
What the evidence adds up to
Salivary gland carcinomas are a heterogeneous group of rare tumours with many histological subtypes, and their low incidence limits study size and the ability to perform phase III trials. Management is not standardised, and patients who do not receive optimal treatment strategies have reduced survival. Surgical resection remains the mainstay of treatment, with radiation and systemic therapy also critical. In a retrospective review of 74 patients with high-risk locally advanced disease treated with surgery and postoperative radiotherapy, the 5-year recurrence-free survival was 49% and the 5-year overall survival was 55%. Advanced nodal classification (N2) was the only significant predictor of both recurrence-free and overall survival, and the authors concluded that long-term survival in this group is unsatisfactory.
Chemotherapy has shown limited activity in patients with metastatic disease, and there is no standard recommendation for its use. In locoregional recurrent or metastatic disease, objective response rates to cytotoxic agents in small phase II studies range from 15% to 50%, with duration of response cited at 6 to 9 months. Given the often indolent nature of the disease, only patients with progressive disease should be enrolled on clinical trials, and study designs must incorporate stringent inclusion criteria to enable accurate reporting of response and disease stabilisation. Recent research has focused on identifying characteristic molecular signatures and genomic alterations in specific histological subtypes, and several signalling pathways have been identified, leading to investigation of a number of targeted therapies.
Despite these efforts, the treatment of salivary gland cancers remains not standardised, and the long-term survival for high-risk locally advanced disease is unsatisfactory. What is still missing are large, coordinated, high-quality clinical trials that can adequately stratify patients by histological subtype and nodal status, and that can rigorously evaluate both established drugs for new indications and novel targeted therapies. Without such trials, the evidence base will remain limited to small retrospective series and modest phase II data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Oncotarget · 2016 · 144 citations · open access
Management of salivary gland carcinomas - a review
Abstract// Xiaoli Wang 1,2 , Yijun Luo 1,2 , Minghuan Li 2 , Hongjiang Yan 2 , Mingping Sun 2 and Tingyong Fan 2 1 School of Medical and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, China 2 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China Correspondence to: Tingyong Fan, email: // Keywords : salivary gland cancers, adenoid cystic carcinoma, elective neck dissection, chemotherapy, targeted therapy Received : June 16, 2016 Accepted : December 08, 2016 Published : December 15, 2016 Abstract Salivary gland carcinomas are a heterogeneous group of tumors with many histological subtypes which occur in both major and minor salivary glands. However, they have a relatively low of incidence. Their rarity limits study size and the ability to perform phase III trials. Therefore, to date, the entire management is usually varied. Certain published studies have paid more attention to the systemic therapy in the management of metastatic or locally recurrent salivary gland cancer, while little effort has been made to study the entire management for this lesions. Although results of treatment for patients with salivary gland carcinoma have improved in recent years, the treatment of salivary gland cancers is still not standardized. And some patients who haven’t received optimal treatment strategies had a reduced survival. In this review, the topics covered include surgery and radiotherapy, selective neck dissection, chemotherapy, and targeted therapy, which aimed to summarize the optimal management approaches and to develop recommendations for managing this lesions. For these rare cancers, there is also a need for a determined, coordinated effort to conduct high-quality clinical trials.
CA A Cancer Journal for Clinicians · 2023 · 52 citations · open access
The evolving landscape of salivary gland tumors
AbstractSalivary gland cancers are a rare, histologically diverse group of tumors. They range from indolent to aggressive and can cause significant morbidity and mortality. Surgical resection remains the mainstay of treatment, but radiation and systemic therapy are also critical parts of the care paradigm. Given the rarity and heterogeneity of these cancers, they are best managed in a multidisciplinary program. In this review, the authors highlight standards of care as well as exciting new research for salivary gland cancers that will strive for better patient outcomes.
Prognostic factors in patients with high‐risk locally advanced salivary gland cancers treated with surgery and postoperative radiotherapy
AbstractBACKGROUND: This study was designed to identify the factors associated with the outcome after standard treatment with surgery and postoperative radiotherapy (RT) for locally advanced salivary gland cancers. METHODS: We conducted a retrospective review of patients with salivary gland cancers registered in the University of Pittsburgh databases from 1990 to 2006. RESULTS: A total of 74 patients were analyzed. Histologic types included salivary duct carcinoma, 24%; adenoid cystic carcinoma, 23%; and adenocarcinoma, 19%; N2, 39%; N0-1, 58%; and major salivary gland origin, 80%. With a median follow-up of 4.1 years, the 5-year recurrence-free survival (RFS) was 49%, and the 5-year overall survival (OS) was 55%. The 5-year local RFS was 76% and the 5-year distant RFS was 60%. Using Cox-regression analysis, advanced N classification (N2) was the only significant predictor of both RFS and OS. CONCLUSION: The long-term survival of patients with high-risk, locally advanced salivary gland cancers is unsatisfactory. Advanced nodal disease is strongly associated with patient outcome and should be considered as a stratification factor in future trials in locally advanced salivary gland cancers.
Advances in oto-rhino-laryngology · 2016 · 3 citations
Chemotherapy and Targeted Therapy
AbstractSalivary gland cancers are uncommon neoplasms of the head and neck that exhibit considerable pathological, biological, and clinical diversity, resulting in a paucity of prospective data regarding the use of non-surgical treatments. Chemotherapy has shown limited activity in patients with metastatic disease, and there has been little exploration of its use in definitive management. There is no standard recommendation for the use of systemic therapy, with palliative chemotherapy being considered on an individual basis for rapidly progressive or symptomatic disease. Recent research has focused on the identification of characteristic molecular signatures and genomic alterations in specific histologic subtypes. Using a molecular biological approach, several signalling pathways have been identified in many cancers of salivary gland origin; thus, a number of targeted therapies have been investigated.
Oncology Reviews · 2011 · 1 citations · open access
Management of salivary gland malignancies: current and developing therapies
AbstractSalivary gland tumors are rare, clinically diverse neoplasms that represent less than 1% of all malignancies. In locoregional recurrent or metastatic disease, systemic therapy is the standard approach. While numerous small phase II studies have evaluated the activity of cytotoxic agents, either alone or in combination, the response rates are generally modest with objective response rates ranging from 15%–50%. Duration of response is cited in the range of 6–9 months. Given this, further evaluation of novel therapies is mandatory in these diseases. With the emergence of molecular targeted therapy, these tumors become optimal candidates for trials of investigational drugs and established drugs for new indications. Of note, given the often indolent nature of disease, only patients with progressive disease should be enrolled and treated on these clinical trials. Study designs must incorporate stringent inclusion criteria to enable accurate reporting of disease response and stabilization. With dedication and co-operation, patients with these rare neoplasms can be accrued to clinical trials and the establishment of new treatment guidelines will be forthcoming.
Research progress of signaling pathways mediating the proliferation, invasion and metastasis of salivary gland adenoid cystic carcinoma
AbstractSalivary gland adenoid cystic carcinoma is one of the most common malignant salivary gland tumors.Its invasion and metastasis are multi-stage and multifactorial processes,in which complex mechanisms and multiple signaling pathways are involved.Here,this article reviews the research progress in signaling pathways of salivary gland adenoid cystic carcinoma.
Key words:
Salivary adenoid cystic carcinoma; Signal path; Cell factor
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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