DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for salivary gland cancer — screening already-approved drugs against its 15-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 cancer maps to a 15-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 cancer 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
HRas proto-oncogene, GTPase (HRAS) — HRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ELT · 1.66 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). 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. A 1978 retrospective analysis of 52 patients reported that 16 of 17 (94%) who received early postoperative radiation therapy were free of local or regional disease 2–14 years later, although 14 were considered high risk for local recurrence; two (12%) developed distant metastases and 14 (82%) were completely disease-free. Survival for patients treated for recurrent or inoperable disease was much worse, with two of 13 disease-free at 45 and 168 months respectively. A 2011 analysis of 74 patients with high-risk locally advanced disease treated with surgery and postoperative radiotherapy found a 5-year recurrence-free survival of 49% and a 5-year overall survival of 55%; advanced nodal classification (N2) was the only significant predictor of both outcomes, and the authors concluded that long-term survival is unsatisfactory.
Chemotherapy has shown limited activity in metastatic disease, and there is no standard recommendation for systemic therapy; palliative chemotherapy is considered on an individual basis for rapidly progressive or symptomatic disease. A 2023 retrospective analysis of 30 patients with incurable advanced salivary gland tumours from a tertiary care centre in India reported that the parotid gland was the most common site (73%), and adenoid cystic carcinoma and salivary duct carcinoma were equally the most common subtypes (37% each). On molecular analysis, salivary duct carcinoma had high rates of androgen receptor positivity (90%) and HER2 positivity (55%). The overall response rate to first-line treatment was 48% (10 of 21 patients), and the median progression-free survival with first-line treatment was 5 months; median overall survival was 10 months. Median overall survival for adenoid cystic carcinoma, salivary duct carcinoma and mucoepidermoid carcinoma were 11, 10 and 7 months respectively, though at 24 months adenoid cystic carcinoma had much higher survival (50%) than the others (10%), indicating a proportion with an indolent course.
Recent research has focused on identifying molecular signatures and genomic alterations in specific histologic subtypes, and several targeted therapies have been investigated. The 2023 analysis noted that a variety of treatment regimens including hormonal therapy, anti-HER2 targeted therapy and chemotherapy were used, but only 9 of 21 patients (43%) went on to receive second-line treatment, with an overall response rate of 44% (4 of 9). What remains missing are high-quality, coordinated clinical trials large enough to test stratified approaches based on histology and molecular markers, as well as prospective data on the use of systemic therapy in definitive management. The rarity of these cancers continues to limit the ability to conduct phase III trials, and no standard recommendation for systemic therapy exists.
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.
Radiation therapy in the treatment of malignant salivary gland tumors
AbstractA retrospective analysis of 52 patients with malignant salivary gland tumors is reported. Seventeen patients received early postoperative radiation therapy and 16 (94%) were free of local or regional disease 2-14 years following initiation of therapy, although 14 were considered at high risk of developing local recurrence. Two subjects (12%) developed distant metastases and 14 (82%) were completely disease-free. Survival and disease-free status of patients treated for recurrent or inoperable disease were much worse with two of 13 disease-free at 45 and 168 months respectively. Various workers have reported recurrence rates after surgery along at 25-38% and over 50% for many histological types. On the basis of this report early postoperative radiation therapy is recommended to reduce the risk of postsurgical recurrence. Prognostic trends relating to both histological type and location of primary disease are discussed.
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.
ecancermedicalscience · 2023 · 2 citations · open access
Incurable advanced salivary gland tumours: a retrospective analysis and peek into the perplexing clinical and molecular intricacies from a tertiary care centre in India
AbstractBackground: Salivary gland tumours are rare cancers with variable course and prognosis. There is a paucity of data, especially for the advanced stages. Materials and methods: This is a retrospective analysis carried out in our institute. All patients seeking treatment for incurable advanced salivary gland tumours from October 2018 to September 2022 were included. Relevant clinical data were collected and appropriate statistical analysis was applied. Results: 30 patients were included in the analysis. The parotid gland was the most common site of origin (73%). Adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC) were equally (37%) the most common pathological subtypes. The majority of patients were males (73%) and lungs (57%) were the most common site of metastases. On molecular analysis, SDC had high rates of androgen receptor (AR) (90%) and human epidermal growth factor receptor 2 (HER2) (55%) positivity. Mucoepidermoid carcinoma (MEC) had AR and HER2 positivity rates of 17% and 20%, respectively, while for ACC it was even lower. A variety of treatment regimens including hormonal therapy, anti-HER2 targeted therapy and chemotherapy were used in first-line treatment. With an overall response rate (ORR) of 10/21 (48%), only 9/21 (43%) went on to receive second-line treatment with an ORR of 4/9 (44%). The progression-free survival (PFS) with first-line treatment (PFS1) was a median of 5 months. The median PFS1 was worst for MEC. The median overall survival (OS) was 10 months. Median OS for ACC, SDC and MEC were 11, 10 and 7 months, respectively. At 24 months, ACC had much higher survival (50%) than others (10%) indicating a proportion of ACC with an indolent course. Conclusion: Our analysis highlights the variable disease biology of advanced salivary gland tumours and throws light on the various possible treatment targets and strategies. Molecular profiling and advancement in targeted therapies are expected to increase survival in this group of rare cancers.
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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