RARE DISEASE
Malignant epithelial tumor of salivary glands
Malignant epithelial tumor of salivary glands
Malignant epithelial tumor of salivary glands
Drug discovery
1
drug
With orphan designation
Overview
Malignant epithelial tumors of the salivary glands are rare, histologically diverse neoplasms, representing <5% of head and neck cancers. Key subtypes include mucoepidermoid carcinoma (29-35%), adenoid cystic carcinoma (20-22%), and salivary duct carcinoma (5-10%) [2][3][15]. Surgical resection is first-line for localized disease, often combined with adjuvant radiotherapy for high-risk features (positive margins, lymph node involvement) [5][8][12]. Advanced/metastatic cases have limited systemic options, driving research into targeted therapies and personalized approaches [2][15].
Therapies
Surgery: Primary treatment with nerve-sparing techniques; neck dissection for nodal involvement [8][12]
Radiation: Adjuvant post-resection (neutron therapy preferred for inoperable cases) [5][14]
Systemic therapy: Limited chemotherapeutic efficacy (ORR 0-70%); anti-androgen therapy emerging for AR+ salivary duct carcinoma [2][12][16]
Categories: rare gastroenterological diseases, rare neoplastic diseases
Research Papers
802 drug discovery papers about Malignant epithelial tumor of salivary glands, with 19 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
802 drug discovery papers about Malignant epithelial tumor of salivary glands, with 19 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
antibodies
2026-09-22 | Durable Intracranial Response to Sacituzumab Tirumotecan in HER2-Negative Salivary Duct Carcinoma With High TROP2 Expression: A Case Report.
Salivary duct carcinoma is an aggressive salivary gland malignancy in which systemic therapy is often guided by androgen receptor and HER2 status. Treatment options are limited for HER2-negative disease after progression on androgen-deprivation therapy and chemotherapy, particularly when active central nervous system (CNS) involvement develops. A 62-year-old man with androgen receptor-positive, HER2-negative salivary duct carcinoma developed progressive intracranial dural metastases involving the left temporal and occipital regions after surgery, adjuvant radiotherapy, androgen-deprivation therapy, and multiple chemotherapy-based regimens. The dominant lesion was a 33.6-mm left temporal dural-based mass extending across the left tentorial leaflet. Immunohistochemical profiling of archival primary tumor tissue showed high membranous TROP2 expression (H-score, 230). Off-label sacituzumab tirumotecan was initiated at 350 mg every 2 weeks without concurrent corticosteroids or local CNS-directed therapy. Serial magnetic resonance imaging demonstrated sustained regression of the dominant left temporal mass from 33.6 to 15.3 mm (-54.5%), with no new intracranial lesions. Intracranial disease control was maintained for approximately 9 months. Treatment-related Grade 2 oral mucositis and leukopenia improved with supportive care and did not require dose reduction or treatment discontinuation. In heavily pretreated, HER2-negative salivary duct carcinoma with high TROP2 expression and progressive intracranial dural metastases, sacituzumab tirumotecan was associated with a durable intracranial response without local CNS-directed therapy. This observation supports further clinical evaluation of TROP2-directed antibody-drug conjugates in salivary duct carcinoma with CNS involvement, while the predictive value of TROP2 expression remains to be established.
2026-08-24 | HER2-positive salivary duct carcinoma: durable response to targeted therapy and chemotherapy.
Salivary duct carcinoma (SDC) of the parotid gland is a rare and aggressive malignancy. Conventional treatment for recurrent or metastatic disease commonly involves platinum-based chemotherapy and taxane-based regimens although treatment is increasingly informed by molecular profiling. A subset of these tumours are human epidermal growth factor receptor 2 (HER2) positive and are associated with more aggressive metastatic behaviour. Novel treatment approaches, particularly dual HER2-targeted therapies commonly used in breast cancer, are now being explored for clinical utility in this group.This case report describes a patient with recurrent metastatic SDC arising from a carcinoma ex-pleomorphic adenoma, with strong HER2 positivity. The patient was treated with a combination of monoclonal antibodies (trastuzumab and pertuzumab) and chemotherapy agents (carboplatin and paclitaxel). The patient demonstrated an excellent and sustained clinical response. This case supports the potential benefit of targeted anti-HER2 therapy in HER2-positive salivary gland tumours and suggests this strategy may be considered in future treatment protocols.
2026-06-05 | Comprehensive management of submandibular salivary duct carcinoma with unilateral axillary lymph node metastasis: a case report.
Salivary duct carcinoma (SDC) is a rare and aggressive malignancy of the salivary glands, most commonly originating in the parotid gland and less frequently in the submandibular gland. Isolated axillary lymph node metastasis is extremely uncommon, and its clinical characteristics and optimal management remain unclear. A 69-year-old man presented with a painless swelling in the left submandibular region. Imaging revealed a submandibular mass with ipsilateral cervical and axillary lymphadenopathy, without distant metastasis. Fine-needle aspiration cytology (FNA cytology) supported the diagnosis of salivary duct carcinoma. The patient underwent left submandibular gland resection with radical neck and axillary lymph node dissection. Histopathology revealed poorly differentiated SDC with metastatic deposits in both cervical and axillary nodes. Genetic testing identified HER2 (ERBB2) gene amplification. Postoperatively, the patient received four cycles of combination chemotherapy with nab-paclitaxel and trastuzumab, followed by one year of trastuzumab maintenance therapy. The treatment was well tolerated, and imaging follow-up at 3, 6, and 12 months showed no recurrence or distant metastasis. Axillary lymph node involvement in submandibular salivary duct carcinoma is extremely rare. To our knowledge, this is the first reported case of isolated unilateral axillary nodal metastasis in the absence of other distant metastases. This case suggests that axillary involvement may represent regional rather than distant spread, and curative surgery remains feasible after comprehensive evaluation. However, this interpretation should be made cautiously because it is based on a single case. Combined chemotherapy and HER2-targeted therapy may achieve favorable short-term outcomes with good tolerability. The accumulation of similar cases is needed to clarify the staging and guide optimal management of such atypical metastases.
2026-05-14 | Parenchymal and stromal adaptations to hypoxia in adenoid cystic carcinoma and mucoepidermoid carcinoma: a comparative immunohistochemical analysis of HIF-1α, NOTCH-1, ADAM-12 and HB-EGF.
To evaluate the expression of hypoxia-inducible factor 1 alpha (HIF-1α), NOTCH-1, ADAM-12, and heparin-binding epidermal growth factor (HB-EGF) in adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and normal salivary glands (SG), exploring hypoxia-related stromal and parenchymal adaptations with potential implications for tumor stratification and therapeutic targeting. Forty-six formalin-fixed, paraffin-embedded samples were analyzed: 17 ACC, 19 MEC, and 10 SG controls. Immunohistochemistry was performed for all markers. Protein expression was quantified as percentage of positive labeling area in both parenchymal and stromal compartments. Statistical comparisons were conducted using the Kruskal-Wallis test followed by Dunn's posthoc test with Holm correction (P < .05). All proteins demonstrated significantly higher parenchymal expression in ACC and MEC compared with SG (all P ≤ .002), without significant differences between tumor types. In the stromal compartment, HB-EGF expression was higher in MEC than ACC (P < .0001), whereas HIF-1α expression was higher in ACC than MEC (P < .0001). ADAM-12 and NOTCH-1 were increased in tumor stroma relative to SG but did not differ between ACC and MEC. Hypoxia-related proteins exhibit compartment-specific patterns that distinguish ACC from MEC at the stromal level, supporting molecular stratification and potential targeted approaches in SG carcinomas.
2026-03-31 | 089 | Epithelial-immune cell crosstalk in salivary gland tumors: implications for tumor progression and diagnostic assessment
Salivary gland tumors (SGTs) comprise a heterogeneous group of epithelial neoplasms with marked histological and biological variability. While most SGTs are benign, malignant forms such as squamous cell carcinoma (SCC) exhibit aggressive behavior, characterized by local invasiveness, early metastasis, and poor response to conventional therapies. A central mechanism in tumor progression is epithelial–mesenchymal transition (EMT), in which epithelial cells lose polarity and intercellular adhesion, acquiring migratory and apoptosis-resistant properties; loss of E-cadherin and increased vimentin expression are key hallmarks of this process. The salivary gland tumor microenvironment plays a critical role in EMT regulation, although the underlying molecular mechanisms remain largely unclear. Among immune components, mast cells have emerged as important modulators through the release of pro-tumorigenic mediators, including mast cell tryptase (MCT), which promotes angiogenesis, extracellular matrix remodeling, and invasive signaling in epithelial cells. In parallel, the inhibitory receptor CD300a, expressed on immune cells and aberrantly on tumor epithelial cells, appears to regulate mast cell degranulation and immune homeostasis within the tumor microenvironment. This study evaluates the histological and immunohistochemical expression of MCT and CD300a in healthy salivary tissues, pleomorphic adenoma, and SCC, focusing on their interplay in EMT regulation and tumor progression. Our findings indicate that mast cell infiltration and MCT release correlate with E-cadherin loss and a more invasive phenotype, while CD300a shows a context-dependent role, exerting predominantly inhibitory effects in benign lesions and pro-tumorigenic functions in malignant tumors. Co-expression of MCT and CD300a in ductal cells may represent a marker of aggressiveness and metastatic potential. Overall, the integrated analysis of MCT and CD300a provides new insights into immune–epithelial interactions in salivary gland tumors and may support the development of therapeutic strategies targeting the tumor microenvironment to counteract EMT and restore tissue homeostasis.
small molecules
2026-09-27 | Diagnostic and Therapeutic Perspectives on Parotid Mammary Analog Secretory Carcinoma: Two Case Reports and Literature Review.
Mammary analog secretory carcinoma (MASC) is a rare malignant tumor of the salivary glands that exhibits significant morphological, immunohistochemical, and molecular similarities with secretory carcinoma of the breast, including the characteristic ETV6-NTRK3 gene fusion. The diagnosis of this condition remains challenging due to its histopathologic overlap with other low-grade salivary gland tumors, such as acinic cell carcinoma and mucoepidermoid carcinoma. The following report details two cases of MASC manifesting in the right parotid gland of a 37-year-old male and a 23-year-old female. Both subjects exhibited slow-growing, painless swellings and radiologic findings indicative of benign lesions. The surgical excision procedure was performed on the first patient via extracapsular dissection, while the second patient underwent superficial parotidectomy. Both procedures were carried out under the supervision of intraoperative facial nerve monitoring. A subsequent histopathological and immunohistochemical examination revealed a glandulocystic growth pattern with eosinophilic secretions and strong immunoreactivity for CK7, S100, and mammaglobin. Although molecular testing for the ETV6-NTRK3 fusion was not performed, the clinical, morphological, and immunophenotypic findings supported the diagnosis of low-grade secretory carcinoma. The patients exhibited uncomplicated recovery, with transient facial nerve paresis in the second patient resolving within 3 months. The first patient remains disease-free after 40 months of clinical and radiological follow-up, while the second patient has shown no evidence of recurrence after 21 months of follow-up. The cases under consideration serve to emphasize the importance of integrating morphology and immunohistochemistry in routine practice, with molecular confirmation remaining the diagnostic gold standard whenever it is available. It is imperative to be aware of this entity to ensure an accurate diagnosis, optimal surgical management, and appropriate long-term surveillance. Emerging evidence suggests that targeted therapy with NTRK inhibitors may represent a promising option for advanced or recurrent disease.
2026-09-11 | Natural products targeting the molecular pathology of salivary gland mucoepidermoid carcinoma: A systematic review of In vitro studies.
Mucoepidermoid carcinoma of the salivary glands has limited systemic treatment options, while natural products have the potential to inhibit tumor survival by modulating multiple molecular pathways. This study aims to elucidate the antitumor activity, biological mechanisms, and translational potential of natural products in a preclinical model of mucoepidermoid carcinoma. A systematic review was conducted in accordance with PRISMA and registered with PROSPERO (CRD420261404862). PubMed, Scopus, ProQuest, ScienceDirect, and Taylor & Francis were searched through July 2026 for studies evaluating the effects of natural products on human mucoepidermoid carcinoma cell lines. Eligibility was based on evidence from human MEC cell-line models in vitro; studies with a corresponding in vivo xenograft component were also eligible, with in vivo findings extracted as supportive translational validation. Data on viability, apoptosis, cell cycle, and molecular pathways were synthesized narratively and mechanistically, while xenograft findings were summarized separately where available. Methodological quality was assessed using QUIN and SciRAP. Fourteen in vitro studies met the inclusion criteria, including four that involved xenograft validation. Overall, the interventions impaired viability or proliferation within a cytotoxic range and primarily induced apoptosis, as evidenced by changes in nuclear morphology, increased Annexin V/PI and sub-G1 fractions, mitochondrial membrane depolarization, caspase activation, and PARP cleavage. A cross-study synthesis revealed mechanistic convergence on ERK/MAPK, Mcl-1, XIAP, and STAT3, linking disruption of survival signaling to mitochondrial apoptosis and the caspase execution phase. Mcl-1 was the most frequently identified anti-apoptotic regulator, while autophagy assessed in two studies demonstrated a cytoprotective function. Heterogeneity in compounds, concentrations, cell lines, and measurement methods hinders comparisons of potency among candidates. Natural products exhibit antiproliferative and proapoptotic activity in a mucoepidermoid carcinoma model by targeting several converging survival pathways. These findings support their development as a source of lead compounds.
2026-09-01 | Therapeutic targeting of E2F inhibits stemness of salivary gland mucoepidermoid carcinoma.
The E2F family of transcription factors plays essential roles in cell cycle regulation, DNA damage response, apoptosis, senescence, glucose metabolism, and angiogenesis. Although E2F pathway alterations were identified across multiple cancers, its role in salivary gland tumorigenesis remains elusive. Given the mechanistic role of E2F in cancer stemness, this pathway represents a promising therapeutic target for salivary malignancies. The purpose of this study was to evaluate the function of E2F1 and E2F4 in the stemness of salivary gland mucoepidermoid carcinoma (MEC), and to test whether pharmacologic inhibition of E2F ablates cancer stem cells (CSC) in MEC. Evaluation of a tissue microarray (TMA) of human MEC samples showed that E2F1 and E2F4 were overexpressed in MECs compared with control salivary glands, where their expression was restricted to ductal cells. CSCs showed higher expression of E2F1 and E2F4 compared to non-CSCs in 3 human MEC cell lines (UM-HMC-1,-3A,-3B). Therapeutic inhibition of E2F with HLM006474 induced expression of p53 and p21 while inhibiting expression of the stemness markers Bmi-1 and ALDH. Notably, the fraction of CSC (ALDHhighCD44high) was significantly reduced by HLM006474 in vitro, and in MEC tumor xenografts in vivo. Collectively, these data demonstrate that E2F inhibits stemness in mucoepidermoid carcinoma and suggest that patients with salivary gland malignancies might benefit from therapeutic inhibition of E2F.
2026-08-28 | Efficacy of S-1 Monotherapy for Salivary Duct Carcinoma With MYC Amplification.
Salivary duct carcinoma (SDC) is a rare, highly aggressive subtype of salivary gland carcinoma, commonly characterized by overexpression of erb-b2 receptor tyrosine kinase 2 [ERBB2, commonly known as human epidermal growth factor receptor 2 (HER2)] and androgen receptor positivity. Anti-HER2 therapy, platinum-based chemotherapy, and androgen-deprivation therapy (ADT) are commonly provided as standard systemic treatments for advanced SDC; however, effective therapeutic options after failure of these treatments remain limited. The clinical efficacy of S-1 monotherapy in SDC and its predictive biomarkers are not well established. Herein, we present a case in which S-1 monotherapy showed efficacy in a case of SDC after resistance to anti-HER2 therapy, platinum-based chemotherapy, and ADT. The patient was a 70-year-old man diagnosed with HER2-positive and androgen receptor-positive SDC of the submandibular gland, who presented with multiple lung metastases. He initially received trastuzumab plus docetaxel as first-line therapy, followed by platinum-based chemotherapy and ADT, but experienced disease progression after each treatment. Comprehensive genomic profiling revealed amplifications of ERBB2 and MYC proto-oncogene bHLH transcription factor (MYC). S-1 monotherapy was started as a late-line therapy. Computed tomography scans 2 months later showed shrinkage of lung and liver metastases, with disease control maintained for more than 5 months. S-1 monotherapy may represent a treatment option for patients with advanced SDC refractory to anti-HER2 therapy, platinum-based chemotherapy, and ADT, particularly in cases harboring MYC amplification.
2026-05-31 | Clinical behavior and predictors of survival in major salivary gland secretory carcinoma.
Secretory carcinoma (formerly mammary analogue secretory carcinoma) is a rare salivary gland malignancy with variable clinical behavior. Due to its rarity, data to guide management is sparse. We describe the clinical behavior and predictors of survival in major salivary gland secretory carcinoma using a cohort of patients from the National Cancer Database (NCDB). Retrospective analysis of patients diagnosed with secretory carcinoma of the major salivary glands between 2011 and 2020. Patients were identified using histology code 8502. Overall survival was assessed using Kaplan-Meier analysis and Cox proportional hazards regression models. 212 patients met criteria for inclusion. There was a slight female predominance with a mean age of 52 years. All patients were treated with surgery with 33% receiving adjuvant therapy.30 patients (14%) had advanced (T3 or T4) primaries while 26 (12%) had regional metastasis. 18% of patients with T2 or worse primary tumors had regional metastasis. 73% of patients with pathologically confirmed nodal metastasis had occult disease. 5-year overall survival was 91.5% with a median follow-up of 58 months.On multivariable analysis, age (adjusted HR 1.06, 95%CI 1.02-1.10, p = 0.005) and advanced primary stage (adjusted HR 3.24, 95%CI 1.10-9.60, p = 0.03) were predictors of worse survival. Occult regional metastasis is common in patients with secretory carcinoma, particularly those with larger primary tumors. Increased age and advanced primaries at presentation are associated with worse overall survival. Further prospective studies are needed to further characterize the behavior of this tumor and determine optimal treatment algorithms.
gene therapies
2024-04-27 | Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors.
Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings.
2021-11-22 | Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping.
Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study clinical, histological, and molecular predictors of survival. One cohort (n = 167), with known CRCT1/3-MAML2 fusion status, was derived from the Hamburg Reference Centre (HRC; graded with the AFIP and Brandwein systems) and the other (n = 384) was derived from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW; graded with the AFIP system). The reliability of both the AFIP and Brandwein grading systems was excellent (n = 155). The weighted kappa for inter-rater agreement was 0.81 (95% CI 0.65-0.97) and 0.83 (95% CI 0.71-0.96) for the AFIP and Brandwein systems, respectively. The 5-year relative survival was 79.7% (95% CI 73.2-86.2%). Although the Brandwein system resulted in a higher rate of G3-MECs, survival in G3-tumors (AFIP or Brandwein grading) was markedly worse than in G1/G2-tumors. Survival in > T2 tumors was markedly worse than in those with lower T-stage. Also, fusion-negative MECs had a worse 5-year progression-free survival. The frequency of fusion-positive MECs in the HRC cohort was 78.4%, of which the majority (86.7%) was G1/G2-tumors. In conclusion, the AFIP and Brandwein systems are useful in estimating prognosis and to guide therapy for G3-MECs. However, their significance regarding young age (≤ 30 years) and location-dependent heterogeneity of in particular G2-tumors is more questionable. We conclude that CRTC1/3-MAML2 testing is a useful adjunct to histologic scoring of MECs and for pinpointing tumors with poor prognosis with higher precision, thus avoiding overtreatment.
2021-10-28 | ETV6-NTRK3-positive parotid mammary analogue secretory carcinoma: a case report.
Mammary analogue secretory carcinoma (MASC) is a recent discovered entity of salivary glands tumors, reported for first time in 2010. The presence of a translocation encodes the ETS variant transcription factor 6-neurotrophic tyrosine receptor kinase (ETV6-NTRK3) gene fusion differences MASC from other tumors. A 68-year-old male showed a non-painful right parotid enlargement, came from dermatology service, and followed by some facial squamous cell carcinomas. A computed tomography (CT) scan showed a 1.7×1.6 cm right parotid enlargement in superficial lobe. The patient underwent a right superficial parotidectomy. The final pathology confirmed the presence of ETV6-NTRK3-positive MASC. Complete right deep parotidectomy and functional cervical emptying were performed. It is necessary to establish an appropriated differential diagnosis between salivary gland tumors. MASC is a low-grade malignancy cancer that sometimes can evolve to a high-grade tumor that might produce local and distance dissemination. Most times, these tumors are only treated by surgical resection and evaluating by a multidisciplinary team the need of more treatments. In our case, the patient showed a primary parotid tumor, removed surgically with free edges, and being identified as MASC. We decided to underwent neck dissection and discovered a second MASC focus on cervical salivary gland; however, there was no nodal dissemination. The patient remains disease-free after 14 months from last surgery. It is important to keep studying genetic therapy targets to ETV6-NTRK3 to obtain a new therapy line to treat those cases that require.
2019-11-15 | Novel gene fusions in secretory carcinoma of the salivary glands: enlarging the ETV6 family.
Secretory carcinoma (SC) of the salivary gland is a low-grade malignancy associated with a well-defined clinical, histologic, immunohistochemical, and cytogenetic signature. Although the t(12;15) (p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion is well documented, advances in molecular profiling in salivary gland tumors have led to the discovery of RET as another ETV6 gene fusion partner in SC. Here, we applied an RNA-based next-generation sequencing (NGS) approach for fusion detection on 14 presumed SC. The cases included 7 SC with classic ETV6-NTRK3 gene fusion and 3 SC harboring ETV6-RET gene fusion. In addition, 2 cases revealed a NCOA4-RET gene fusion and were subsequently reclassified as intraductal carcinomas. One case with an unusual dual-pattern morphology revealed a novel translocation involving ETV6, NTRK3, and MAML3 gene rearrangements. Interestingly, no ETV6-NTRK3 or ETV6-RET SC was ever documented to have this unique dual-pattern morphology or harbor a MAML3 mutation. The remaining case had no detected chromosomal abnormalities. Advances in molecular profiling of SC have led to the discovery of novel fusion partners such as RET and now MAML3. Further molecular characterization of salivary gland neoplasms is needed as these mutations may present alternative therapeutic targets in patients with these tumors.
2016-10-12 | Type III TGF-β receptor inhibits cell proliferation and migration in salivary glands adenoid cystic carcinoma by suppressing NF-κB signaling.
It is known that the TGF-β superfamily receptors act as master regulators of cancer progression. However, alteration and role of type III TGF-β receptor (TβRIII, or betaglycan) as the most abundant of the TGF-β receptor has not been explored in salivary gland adenoid cystic carcinoma (ACC). Here, we reported that tumor biopsies and matched normal human salivary glands from patients with ACC were examined for the expression of TβRIII. The expression of TβRIII protein is significantly decreased in ACC patients based on immunohistochemistry and western blot analysis. In vitro, a transient overexpression of TβRIII markedly induced apoptosis and cell cycle arrest in the G2/M phase, thereby inhibited cell viability and migration of ACC-M cells. Co-immunoprecipitation revealed that TβRIII, scaffolding protein-arrestin2 (β-arrestin2) and IκBα formed a complex. Transient overexpression of TβRIII decreased p-p65 expression and increased IκBα expression, which was abolished by knockdown of β-arrestin2. The present study defines TβRIII as a biomarker exerting antitumor action on ACC progression.Gene therapy of TβRIII may be a powerful new approach for ACC disease.
oligonucleotides
2026-02-02 | NDC80 kinetochore complex component is a potential molecular target of adenoid cystic carcinoma.
Adenoid cystic carcinoma (ACC) is a slow-growing malignant tumour that primarily originates from the major and minor salivary glands. The relationship between the NDC80 kinetochore complex component (NUF2) and ACC remains to be elucidated. The present study obtained gene expression information from the Gene Expression Omnibus database (GSE88804 and GSE153002). Differentially expressed genes were identified by using the 'limma' package in R. A protein-protein interaction network was constructed with the Search Tool for Retrieval of Interacting Genes/Proteins database and key genes were extracted using Cytoscape software. Analysis of differential expression levels of hub genes in tumour and normal tissue was performed using Tumour Immune Estimation Resource (TIMER) and GSE36820 profiles. Gene Ontology enrichment was subsequently analysed based on differences in NUF2 expression in tumour tissues. In addition, single sample Gene Set Enrichment Analysis (ssGSEA) was used for the quantitative analysis of immune cell infiltration in ACC. Western blotting and immunohistochemistry were used to assess NUF2 expression levels in tumour and adjacent non-tumour tissues. Small interfering RNA (siRNA) was used to decrease NUF2 expression in ACC cell lines. The biological functions of NUF2 were analysed using Cell Counting Kit-8 and wound healing assays. A total of 248 differential genes were identified by differential expression analyses, with 113 genes upregulated and 135 downregulated. A total of 7 hub genes, namely, CDK1, budding uninhibited by benzimidazoles 1 mitotic checkpoint serine/threonine kinase B, DNA topoisomerase II α, cyclin B2, NUF2, budding uninhibited by benzimidazoles 1 and centromere protein F, were obtained using the 'cytoHubba' plugin. The TIMER, standardized and GSE36820 databases revealed that the expression levels of NUF2 were higher in ACC tissues compared with normal tissue samples. Western blotting and immunohistochemical staining of ACC tissues provided evidence of NUF2 upregulation in ACC tissue compared with normal tissue. NUF2-related genes were enriched in 'ameboidal-type cell migration', 'collagen-containing extracellular matrix' and 'actin binding'. ssGSEA analysis revealed that the expression level of NUF2 was notably associated with activated CD4+ T cells, memory B cell and plasmacytoid dendritic cell. ACC cells transfected with NUF2 siRNA exhibited decreased proliferation and migration compared with the control. In conclusion, NUF2 is upregulated in ACC and is associated with immune cell infiltration. Functional studies demonstrated that NUF2 promotes ACC cell proliferation and migration, suggesting its potential as a therapeutic target for ACC.
2024-02-26 | Dynamic Role of miRNAs in Salivary Gland Carcinomas: From Biomarkers to Therapeutic Targets.
Salivary gland carcinomas (SGCs) are a rare group of malignant neoplasms of the head and neck region. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been associated with the control biological process and oncogenic mechanism by the regulation of gene expression at the post-transcriptional level. Recent evidence has suggested that miRNA expression may play a role in the tumorigenesis and carcinogenesis process in SGCs. This review provides a comprehensive literature review of the role of miRNAs expression in SGCs focusing on the diagnostic, prognostic, and therapeutic applications. In this review, numerous dysregulated miRNAs have demonstrated an oncogenic and suppressor role in SGCs. In the future, these miRNAs may eventually constitute useful diagnostic and prognostic biomarkers that may lead to a better understanding of SGCs oncogenesis. Additionally, the development of therapeutic agents based on miRNAs may be a promising target in SGC treatment.
2023-05-12 | Single-cell RNA sequencing reveals the heterogeneity and microenvironment in one adenoid cystic carcinoma sample.
Adenoid cystic carcinoma (ACC) is one of the most common malignancy of the major salivary glands with a high recurrence rate and poor prognosis. Determining tumor heterogeneity and factors in the microenvironment may provide novel therapeutic targets for ACC. We performed single-cell RNA sequencing of one ACC sample and normal salivary gland tissues from a patient to analyze tumor heterogeneity, immunosuppressive landscape, and intercellular communication networks. The heterogeneity of epithelial cells in ACC tissues was significantly higher compared with that in normal tissues, whereas immune cells were almost absent. We found four malignant cell clusters in ACC and explored their characteristics and function. In tumor tissues, CD8 + cytotoxic T cells and CD4 + T helper cells were significantly decreased, whereas IgA + plasma cells were absent. There were two clusters of macrophages, one representing IL1B macrophages and the other consisted of a cluster of macrophages associated with the epithelial mesenchymal transition (EMT). Both were significantly different from the normal tissue composition. In addition, the communication between epithelial cells and other cells in the tumor tissue was enhanced. MIF-CD74 and APP-CD74 were significantly upregulated. We comprehensively described the heterogeneity of ACC and the tumor microenvironment (TME) from a single cell perspective including cell characteristics, immune cell infiltration, and cell communication. CLINICAL RELEVANCE: This study provided further insights into ACC and may lead to new treatment strategies.
2022-12-23 | Overexpression of LAG3, TIM3, and A2aR in adenoid cystic carcinoma and mucoepidermoid carcinoma.
Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the two most frequent malignancies of salivary glands. This study aims to explore the expression and migration of LAG3, TIM3, and A2aR in AdCC and MEC, and the potential relationship with oncogenic signaling molecules and immunosuppressive cytokines. Custom made human salivary gland tissue microarrays included 81 AdCCs, 52 MECs, 76 normal salivary glands (NSG), and 14 pleomorphic adenoma (PMA) samples. Immunohistochemical analysis of lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), adenosine 2a receptor (A2aR), oncogenic phosphorylated S6 kinase (p-S6) and ERK1/2 (p-ERK1/2 ), and TGF-β1 was performed with salivary gland tissue microarrays of human samples. The correlation of the immunostaining was analyzed based on a digital pathological system, and data were evaluated by hierarchical cluster. Further in vitro studies of knockdown immune checkpoints LAG3, TIM3, and A2aR were carried out by siRNA transfection. The expression levels of LAG3, TIM3, and A2aR were remarkably increased in AdCC and MEC, compared with NSG and PMA samples, but were independent of pathology grade. They were closely correlated with TGF-β1, slightly related to p-ERK1/2 and p-S6. After the knockdown of immune checkpoints LAG3, TIM3, and A2aR, the migration of SACC-LM cell line was significantly reduced. These results suggested that LAG3, TIM3, and A2aR are overexpressed in AdCC and MEC, may promote migration of SACC-LM cell and correlated with TGF-β1 and oncogenic signaling pathways.
2021-02-04 | Metallothionein Expression and its Influence on the In Vitro Biological Behavior of Mucoepidermoid Carcinoma.
Mucoepidermoid carcinoma (MEC) is the most common tumor in the salivary glands, often presenting with recurrence and metastasis due to its high invasive capacity. Metallothionein (MT), a zinc storage protein that supplies this element for protease activity, is probably related to mucoepidermoid carcinoma behavior. This prompted us to characterize a cell line derived from mucoepidermoid carcinoma and to correlate metallothionein expression with transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α) and matrix metalloproteinases (MMPs). Transcriptomic analysis and cytogenetic assays were performed to detect the expression of genes of interest and cellular chromosomal alterations, respectively. MEC cells with a depleted metallothionein 2A (MT2A) gene were subjected to Western blot to correlate metallothionein expression with growth factors and MMPs. Additionally, cells with depleted MT were subjected to migration and invasion assays. The transcriptomic study revealed reads mapped to cytokeratins 19 and AE1/AE3, α-smooth muscle actin, vimentin, and fibronectin. Cytogenetic evaluation demonstrated structural and numerical alterations, including the translocation t(11;19)(q21;p13), characteristic of MEC. Metallothionein depletion was correlated with the decreased expression of TGF-α and MMP-9, while TNF-α protein levels were augmented. Migration and invasion activity were diminished after metallothionein silencing. Our findings suggest an important role of MT in MEC invasion, through the regulation of proteins involved in this process.
other
2025-10-01 | Construction And Molecular Characterization Of Rare Salivary Gland Tumor Organoids
To establish a personalized research model for rare subtypes of salivary gland tumor, bridging foundational investigations and clinical applications to advance precision oncology in this understudied field. Sample Collection Rare salivary gland tumor tissuescollected under sterile protocols. Ethics: Approved by IRB of China Medical University Hospital of Stomatology (#2025010). Clinical Data Integration Statistical analysis of clinical metadata and organoid parameters. Organoid Histological Evaluation Assessment: Inverted microscopy, H&E/immunofluorescence staining (lineage-specific markers). Morphometric/molecular comparisons to parental tumors using non-parametric tests. Transcriptomic Profiling RNA-seq: Tumor tissues, normal glands, and organoids. Bioinformatics: Dimensionality reduction, consensus clustering (Consensus Cluster Plus), differential expression (DESeq2). 1.Organoid models for six rare salivary gland tumor subtypes—including two benign (myoepithelioma [ME] and canalicular adenoma [CA]) and four malignant (epithelial-myoepithelial carcinoma [EMC], myoepithelial carcinoma [MC], secretory carcinoma [SC], and nonspecific adenocarcinoma [NOS])—were successfully established alongside normal gland organoid controls, demonstrating rapid maturation by day 14 and growth plateauing at day 21. 2.Organoids derived from myoepithelial-dominant tumors (ME, MC) showed reduced proliferation efficiency, while others exhibited robust expansion. 3.These organoids faithfully retained parental tumor morphology, transcriptional profiles and cellular heterogeneity mirroring diagnostic and structural features of original tumors. Salivary gland tumor organoids serve as high-fidelity in vitro models for studying rare salivary gland tumors, effectively recapitulating the morphological and molecular characteristics of their parental tumors offering a powerful platform to advance personalized therapeutic strategies and mechanistic studies for rare salivary gland carcinomas.
2025-04-17 | Integrative genomic pan-cancer analysis reveals the prognostic significance of DEFB1 in tumors.
Defensin beta 1 (DEFB1) is a key immune response gene, but its role in cancer remains unclear. This study aims to explore DEFB1 expression, genetic alterations, immune infiltration, and prognostic significance across various cancer types. We analyzed DEFB1 expression and its association with cancer prognosis using data from public platforms, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA). Additionally, we examined DEFB1 genetic alterations, immune cell infiltration, and its molecular partners using various bioinformatics tools. DEFB1 expression was highest in salivary glands, kidneys, and pancreas. In cancers, DEFB1 was upregulated in cholangiocarcinoma, kidney chromophobe, and melanoma, but downregulated in breast, colon, and rectal cancers. High DEFB1 expression was linked to poorer overall survival in lung adenocarcinoma and pancreatic adenocarcinoma, but better survival in head and neck squamous cell carcinoma. Genetic analysis revealed alterations in liver and gastric cancers. Immune infiltration analysis showed a correlation between DEFB1 and cancer-associated fibroblasts in liver cancer, while neutrophil infiltration was linked to bladder carcinoma, diffuse large B-cell lymphoma, and lung squamous cell carcinoma. Key genes associated with DEFB1 included KLK1, BSND, and CLCNKB. This study highlights DEFB1's potential as a prognostic biomarker and its influence on the tumor immune microenvironment across different cancers. These findings suggest DEFB1 could be a target for future cancer therapies, although further studies are needed to validate these results.
2024-09-07 | Functional reconstruction of tissue defects after total parotidectomy using a modified submandibular gland flap.
Reconstruction of soft tissue defects after total parotidectomy requires a feasible and effective pedicled flap with sufficient volume. In this study, we introduce a modified submandibular gland flap (SMGF) for functional reconstruction of soft tissue defects resulting from total parotidectomy. This study included 12 patients diagnosed with parotid gland carcinoma undergoing total parotidectomy and ipsilateral selective neck dissection. The modified SMGF was harvested and transferred to the parotid bed. This procedure was coupled with anastomosis between the parotid gland duct and Wharton's duct. The feasibility of the surgery, postoperative complications, facial profile restoration, and salivary secretion were assessed. All SMGFs pedicled only over the proximal facial artery survived without major complications. Facial profiles were well-restored, and salivary secretion was partially reserved. During the postoperative follow-up, no tumor recurrence was observed in any of the cases, and the volume of the SMGFs did not show obvious atrophy. The modified SMGF is a viable solution for volume restoration and functional reconstruction after total parotidectomy. This modified technique is simple and feasible for the functional reconstruction of soft tissue defects after total parotidectomy compared to other flaps and is worthy of clinical promotion.
2024-08-29 | Establishment and characterization of cMYB-expressing human salivary adenoid cystic carcinoma cell lines (UM-HACC-14, UM-HACC-6) and matching patient-derived xenograft model (UM-PDX-HACC-14).
Limited availability of authentic human adenoid cystic carcinoma (ACC) cell lines has hindered progress in understanding mechanisms underpinning the biology of this disease and the development of safe and effective therapies. Surgical human ACC specimens (UM-HACC-6, UM-HACC-14) were dissociated into single cell suspensions and cultured in fibronectin-coated flasks. Alternatively, tumor fragments were transplanted subcutaneously into female immunodeficient (SCID) mice to establish patient-derived xenograft tumors (PDX; UM-PDX-HACC-14). Both ACC cell lines showed continuous growth in monolayers for over 100 passages. Total RNA-Seq, RT-PCR, and FISH analysis revealed that both are MYB-NFIB fusion negative. Western blots revealed passage-dependent expression of E-Cadherin, PCNA, p63, phospho-c-MYB, and NFIB. Both, UM-HACC-14 and UM-HACC-6 cells exhibited tumorigenic potential when injected orthotopically into mouse submandibular glands. UM-HACC-14, patient-matching UM-PDX-HACC-14, and the UM-HACC-6 cell line are new, authenticated preclinical models of ACC that are well suited for mechanistic and developmental therapeutics studies.
2023-11-16 | Identifying potential immuno-oncology targets in salivary gland mucoepidermoid carcinoma based on inflammatory status and treatment response.
Mucoepidermoid carcinoma is a rare salivary gland malignant tumour. This study aimed to investigate inflammatory and immune signatures of mucoepidermoid carcinoma by identifying potential proteo-transcriptomic biomarkers towards the development of precision immuno-oncology treatment strategies. A total of 30 biopsies obtained from patients diagnosed with mucoepidermoid carcinoma between 2013 and 2022 were analysed after H&E staining for scoring of histological inflammatory stroma subtypes and inflammatory hotspots with QuPath. Multiplex immunofluorescence staining and NanoString nCounter PanCancer IO 360™ panel were used to assess stroma and tumour inflammation signatures in high grade mucoepidermoid carcinoma cases in the tumour microenvironment via proteomics and transcriptomics, respectively. Inflammatory cells within the histological inflammatory stroma inflammatory (HIS-INF/hot) tumour neighbourhoods were greater compared to the histological inflammatory stroma-immune desert (HIS-ID/cold) (p = 0.001). A similar trend was observed between treatment non-responders and responders in stroma neighbourhoods (p = 0.0625) and in stroma-to-interface inflammatory hotspots (p = 0.0081), indicating an augmented inflammatory response in hot tumours and non-responders. Furthermore, there were striking differences in the expression of pan-immune leukocyte marker CD45 between responders and non responders particularly in the tumour neighbourhoods (p = 0.0341), but such were not robust for PD-1 and macrophage fractions. Additionally, transcriptomic analysis revealed key differences in leukocyte activation profiles between responders and non-responders. This preliminary report unveils the importance of assessing immune leukocyte cellular fractions and pathways for future prognostic biomarker discoveries in mucoepidermoid carcinoma as per the involvement of CD45-driven inflammatory and immune mediators in high grade mucoepidermoid carcinoma in non-responders to treatment. These findings will potentially contribute to the development of novel personalised immunotherapies.
antibodies
2026-09-22 | Durable Intracranial Response to Sacituzumab Tirumotecan in HER2-Negative Salivary Duct Carcinoma With High TROP2 Expression: A Case Report.
Salivary duct carcinoma is an aggressive salivary gland malignancy in which systemic therapy is often guided by androgen receptor and HER2 status. Treatment options are limited for HER2-negative disease after progression on androgen-deprivation therapy and chemotherapy, particularly when active central nervous system (CNS) involvement develops. A 62-year-old man with androgen receptor-positive, HER2-negative salivary duct carcinoma developed progressive intracranial dural metastases involving the left temporal and occipital regions after surgery, adjuvant radiotherapy, androgen-deprivation therapy, and multiple chemotherapy-based regimens. The dominant lesion was a 33.6-mm left temporal dural-based mass extending across the left tentorial leaflet. Immunohistochemical profiling of archival primary tumor tissue showed high membranous TROP2 expression (H-score, 230). Off-label sacituzumab tirumotecan was initiated at 350 mg every 2 weeks without concurrent corticosteroids or local CNS-directed therapy. Serial magnetic resonance imaging demonstrated sustained regression of the dominant left temporal mass from 33.6 to 15.3 mm (-54.5%), with no new intracranial lesions. Intracranial disease control was maintained for approximately 9 months. Treatment-related Grade 2 oral mucositis and leukopenia improved with supportive care and did not require dose reduction or treatment discontinuation. In heavily pretreated, HER2-negative salivary duct carcinoma with high TROP2 expression and progressive intracranial dural metastases, sacituzumab tirumotecan was associated with a durable intracranial response without local CNS-directed therapy. This observation supports further clinical evaluation of TROP2-directed antibody-drug conjugates in salivary duct carcinoma with CNS involvement, while the predictive value of TROP2 expression remains to be established.
2026-08-24 | HER2-positive salivary duct carcinoma: durable response to targeted therapy and chemotherapy.
Salivary duct carcinoma (SDC) of the parotid gland is a rare and aggressive malignancy. Conventional treatment for recurrent or metastatic disease commonly involves platinum-based chemotherapy and taxane-based regimens although treatment is increasingly informed by molecular profiling. A subset of these tumours are human epidermal growth factor receptor 2 (HER2) positive and are associated with more aggressive metastatic behaviour. Novel treatment approaches, particularly dual HER2-targeted therapies commonly used in breast cancer, are now being explored for clinical utility in this group.This case report describes a patient with recurrent metastatic SDC arising from a carcinoma ex-pleomorphic adenoma, with strong HER2 positivity. The patient was treated with a combination of monoclonal antibodies (trastuzumab and pertuzumab) and chemotherapy agents (carboplatin and paclitaxel). The patient demonstrated an excellent and sustained clinical response. This case supports the potential benefit of targeted anti-HER2 therapy in HER2-positive salivary gland tumours and suggests this strategy may be considered in future treatment protocols.
2026-06-05 | Comprehensive management of submandibular salivary duct carcinoma with unilateral axillary lymph node metastasis: a case report.
Salivary duct carcinoma (SDC) is a rare and aggressive malignancy of the salivary glands, most commonly originating in the parotid gland and less frequently in the submandibular gland. Isolated axillary lymph node metastasis is extremely uncommon, and its clinical characteristics and optimal management remain unclear. A 69-year-old man presented with a painless swelling in the left submandibular region. Imaging revealed a submandibular mass with ipsilateral cervical and axillary lymphadenopathy, without distant metastasis. Fine-needle aspiration cytology (FNA cytology) supported the diagnosis of salivary duct carcinoma. The patient underwent left submandibular gland resection with radical neck and axillary lymph node dissection. Histopathology revealed poorly differentiated SDC with metastatic deposits in both cervical and axillary nodes. Genetic testing identified HER2 (ERBB2) gene amplification. Postoperatively, the patient received four cycles of combination chemotherapy with nab-paclitaxel and trastuzumab, followed by one year of trastuzumab maintenance therapy. The treatment was well tolerated, and imaging follow-up at 3, 6, and 12 months showed no recurrence or distant metastasis. Axillary lymph node involvement in submandibular salivary duct carcinoma is extremely rare. To our knowledge, this is the first reported case of isolated unilateral axillary nodal metastasis in the absence of other distant metastases. This case suggests that axillary involvement may represent regional rather than distant spread, and curative surgery remains feasible after comprehensive evaluation. However, this interpretation should be made cautiously because it is based on a single case. Combined chemotherapy and HER2-targeted therapy may achieve favorable short-term outcomes with good tolerability. The accumulation of similar cases is needed to clarify the staging and guide optimal management of such atypical metastases.
2026-05-14 | Parenchymal and stromal adaptations to hypoxia in adenoid cystic carcinoma and mucoepidermoid carcinoma: a comparative immunohistochemical analysis of HIF-1α, NOTCH-1, ADAM-12 and HB-EGF.
To evaluate the expression of hypoxia-inducible factor 1 alpha (HIF-1α), NOTCH-1, ADAM-12, and heparin-binding epidermal growth factor (HB-EGF) in adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and normal salivary glands (SG), exploring hypoxia-related stromal and parenchymal adaptations with potential implications for tumor stratification and therapeutic targeting. Forty-six formalin-fixed, paraffin-embedded samples were analyzed: 17 ACC, 19 MEC, and 10 SG controls. Immunohistochemistry was performed for all markers. Protein expression was quantified as percentage of positive labeling area in both parenchymal and stromal compartments. Statistical comparisons were conducted using the Kruskal-Wallis test followed by Dunn's posthoc test with Holm correction (P < .05). All proteins demonstrated significantly higher parenchymal expression in ACC and MEC compared with SG (all P ≤ .002), without significant differences between tumor types. In the stromal compartment, HB-EGF expression was higher in MEC than ACC (P < .0001), whereas HIF-1α expression was higher in ACC than MEC (P < .0001). ADAM-12 and NOTCH-1 were increased in tumor stroma relative to SG but did not differ between ACC and MEC. Hypoxia-related proteins exhibit compartment-specific patterns that distinguish ACC from MEC at the stromal level, supporting molecular stratification and potential targeted approaches in SG carcinomas.
2026-03-31 | 089 | Epithelial-immune cell crosstalk in salivary gland tumors: implications for tumor progression and diagnostic assessment
Salivary gland tumors (SGTs) comprise a heterogeneous group of epithelial neoplasms with marked histological and biological variability. While most SGTs are benign, malignant forms such as squamous cell carcinoma (SCC) exhibit aggressive behavior, characterized by local invasiveness, early metastasis, and poor response to conventional therapies. A central mechanism in tumor progression is epithelial–mesenchymal transition (EMT), in which epithelial cells lose polarity and intercellular adhesion, acquiring migratory and apoptosis-resistant properties; loss of E-cadherin and increased vimentin expression are key hallmarks of this process. The salivary gland tumor microenvironment plays a critical role in EMT regulation, although the underlying molecular mechanisms remain largely unclear. Among immune components, mast cells have emerged as important modulators through the release of pro-tumorigenic mediators, including mast cell tryptase (MCT), which promotes angiogenesis, extracellular matrix remodeling, and invasive signaling in epithelial cells. In parallel, the inhibitory receptor CD300a, expressed on immune cells and aberrantly on tumor epithelial cells, appears to regulate mast cell degranulation and immune homeostasis within the tumor microenvironment. This study evaluates the histological and immunohistochemical expression of MCT and CD300a in healthy salivary tissues, pleomorphic adenoma, and SCC, focusing on their interplay in EMT regulation and tumor progression. Our findings indicate that mast cell infiltration and MCT release correlate with E-cadherin loss and a more invasive phenotype, while CD300a shows a context-dependent role, exerting predominantly inhibitory effects in benign lesions and pro-tumorigenic functions in malignant tumors. Co-expression of MCT and CD300a in ductal cells may represent a marker of aggressiveness and metastatic potential. Overall, the integrated analysis of MCT and CD300a provides new insights into immune–epithelial interactions in salivary gland tumors and may support the development of therapeutic strategies targeting the tumor microenvironment to counteract EMT and restore tissue homeostasis.
small molecules
2026-09-27 | Diagnostic and Therapeutic Perspectives on Parotid Mammary Analog Secretory Carcinoma: Two Case Reports and Literature Review.
Mammary analog secretory carcinoma (MASC) is a rare malignant tumor of the salivary glands that exhibits significant morphological, immunohistochemical, and molecular similarities with secretory carcinoma of the breast, including the characteristic ETV6-NTRK3 gene fusion. The diagnosis of this condition remains challenging due to its histopathologic overlap with other low-grade salivary gland tumors, such as acinic cell carcinoma and mucoepidermoid carcinoma. The following report details two cases of MASC manifesting in the right parotid gland of a 37-year-old male and a 23-year-old female. Both subjects exhibited slow-growing, painless swellings and radiologic findings indicative of benign lesions. The surgical excision procedure was performed on the first patient via extracapsular dissection, while the second patient underwent superficial parotidectomy. Both procedures were carried out under the supervision of intraoperative facial nerve monitoring. A subsequent histopathological and immunohistochemical examination revealed a glandulocystic growth pattern with eosinophilic secretions and strong immunoreactivity for CK7, S100, and mammaglobin. Although molecular testing for the ETV6-NTRK3 fusion was not performed, the clinical, morphological, and immunophenotypic findings supported the diagnosis of low-grade secretory carcinoma. The patients exhibited uncomplicated recovery, with transient facial nerve paresis in the second patient resolving within 3 months. The first patient remains disease-free after 40 months of clinical and radiological follow-up, while the second patient has shown no evidence of recurrence after 21 months of follow-up. The cases under consideration serve to emphasize the importance of integrating morphology and immunohistochemistry in routine practice, with molecular confirmation remaining the diagnostic gold standard whenever it is available. It is imperative to be aware of this entity to ensure an accurate diagnosis, optimal surgical management, and appropriate long-term surveillance. Emerging evidence suggests that targeted therapy with NTRK inhibitors may represent a promising option for advanced or recurrent disease.
2026-09-11 | Natural products targeting the molecular pathology of salivary gland mucoepidermoid carcinoma: A systematic review of In vitro studies.
Mucoepidermoid carcinoma of the salivary glands has limited systemic treatment options, while natural products have the potential to inhibit tumor survival by modulating multiple molecular pathways. This study aims to elucidate the antitumor activity, biological mechanisms, and translational potential of natural products in a preclinical model of mucoepidermoid carcinoma. A systematic review was conducted in accordance with PRISMA and registered with PROSPERO (CRD420261404862). PubMed, Scopus, ProQuest, ScienceDirect, and Taylor & Francis were searched through July 2026 for studies evaluating the effects of natural products on human mucoepidermoid carcinoma cell lines. Eligibility was based on evidence from human MEC cell-line models in vitro; studies with a corresponding in vivo xenograft component were also eligible, with in vivo findings extracted as supportive translational validation. Data on viability, apoptosis, cell cycle, and molecular pathways were synthesized narratively and mechanistically, while xenograft findings were summarized separately where available. Methodological quality was assessed using QUIN and SciRAP. Fourteen in vitro studies met the inclusion criteria, including four that involved xenograft validation. Overall, the interventions impaired viability or proliferation within a cytotoxic range and primarily induced apoptosis, as evidenced by changes in nuclear morphology, increased Annexin V/PI and sub-G1 fractions, mitochondrial membrane depolarization, caspase activation, and PARP cleavage. A cross-study synthesis revealed mechanistic convergence on ERK/MAPK, Mcl-1, XIAP, and STAT3, linking disruption of survival signaling to mitochondrial apoptosis and the caspase execution phase. Mcl-1 was the most frequently identified anti-apoptotic regulator, while autophagy assessed in two studies demonstrated a cytoprotective function. Heterogeneity in compounds, concentrations, cell lines, and measurement methods hinders comparisons of potency among candidates. Natural products exhibit antiproliferative and proapoptotic activity in a mucoepidermoid carcinoma model by targeting several converging survival pathways. These findings support their development as a source of lead compounds.
2026-09-01 | Therapeutic targeting of E2F inhibits stemness of salivary gland mucoepidermoid carcinoma.
The E2F family of transcription factors plays essential roles in cell cycle regulation, DNA damage response, apoptosis, senescence, glucose metabolism, and angiogenesis. Although E2F pathway alterations were identified across multiple cancers, its role in salivary gland tumorigenesis remains elusive. Given the mechanistic role of E2F in cancer stemness, this pathway represents a promising therapeutic target for salivary malignancies. The purpose of this study was to evaluate the function of E2F1 and E2F4 in the stemness of salivary gland mucoepidermoid carcinoma (MEC), and to test whether pharmacologic inhibition of E2F ablates cancer stem cells (CSC) in MEC. Evaluation of a tissue microarray (TMA) of human MEC samples showed that E2F1 and E2F4 were overexpressed in MECs compared with control salivary glands, where their expression was restricted to ductal cells. CSCs showed higher expression of E2F1 and E2F4 compared to non-CSCs in 3 human MEC cell lines (UM-HMC-1,-3A,-3B). Therapeutic inhibition of E2F with HLM006474 induced expression of p53 and p21 while inhibiting expression of the stemness markers Bmi-1 and ALDH. Notably, the fraction of CSC (ALDHhighCD44high) was significantly reduced by HLM006474 in vitro, and in MEC tumor xenografts in vivo. Collectively, these data demonstrate that E2F inhibits stemness in mucoepidermoid carcinoma and suggest that patients with salivary gland malignancies might benefit from therapeutic inhibition of E2F.
2026-08-28 | Efficacy of S-1 Monotherapy for Salivary Duct Carcinoma With MYC Amplification.
Salivary duct carcinoma (SDC) is a rare, highly aggressive subtype of salivary gland carcinoma, commonly characterized by overexpression of erb-b2 receptor tyrosine kinase 2 [ERBB2, commonly known as human epidermal growth factor receptor 2 (HER2)] and androgen receptor positivity. Anti-HER2 therapy, platinum-based chemotherapy, and androgen-deprivation therapy (ADT) are commonly provided as standard systemic treatments for advanced SDC; however, effective therapeutic options after failure of these treatments remain limited. The clinical efficacy of S-1 monotherapy in SDC and its predictive biomarkers are not well established. Herein, we present a case in which S-1 monotherapy showed efficacy in a case of SDC after resistance to anti-HER2 therapy, platinum-based chemotherapy, and ADT. The patient was a 70-year-old man diagnosed with HER2-positive and androgen receptor-positive SDC of the submandibular gland, who presented with multiple lung metastases. He initially received trastuzumab plus docetaxel as first-line therapy, followed by platinum-based chemotherapy and ADT, but experienced disease progression after each treatment. Comprehensive genomic profiling revealed amplifications of ERBB2 and MYC proto-oncogene bHLH transcription factor (MYC). S-1 monotherapy was started as a late-line therapy. Computed tomography scans 2 months later showed shrinkage of lung and liver metastases, with disease control maintained for more than 5 months. S-1 monotherapy may represent a treatment option for patients with advanced SDC refractory to anti-HER2 therapy, platinum-based chemotherapy, and ADT, particularly in cases harboring MYC amplification.
2026-05-31 | Clinical behavior and predictors of survival in major salivary gland secretory carcinoma.
Secretory carcinoma (formerly mammary analogue secretory carcinoma) is a rare salivary gland malignancy with variable clinical behavior. Due to its rarity, data to guide management is sparse. We describe the clinical behavior and predictors of survival in major salivary gland secretory carcinoma using a cohort of patients from the National Cancer Database (NCDB). Retrospective analysis of patients diagnosed with secretory carcinoma of the major salivary glands between 2011 and 2020. Patients were identified using histology code 8502. Overall survival was assessed using Kaplan-Meier analysis and Cox proportional hazards regression models. 212 patients met criteria for inclusion. There was a slight female predominance with a mean age of 52 years. All patients were treated with surgery with 33% receiving adjuvant therapy.30 patients (14%) had advanced (T3 or T4) primaries while 26 (12%) had regional metastasis. 18% of patients with T2 or worse primary tumors had regional metastasis. 73% of patients with pathologically confirmed nodal metastasis had occult disease. 5-year overall survival was 91.5% with a median follow-up of 58 months.On multivariable analysis, age (adjusted HR 1.06, 95%CI 1.02-1.10, p = 0.005) and advanced primary stage (adjusted HR 3.24, 95%CI 1.10-9.60, p = 0.03) were predictors of worse survival. Occult regional metastasis is common in patients with secretory carcinoma, particularly those with larger primary tumors. Increased age and advanced primaries at presentation are associated with worse overall survival. Further prospective studies are needed to further characterize the behavior of this tumor and determine optimal treatment algorithms.
gene therapies
2024-04-27 | Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors.
Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings.
2021-11-22 | Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping.
Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study clinical, histological, and molecular predictors of survival. One cohort (n = 167), with known CRCT1/3-MAML2 fusion status, was derived from the Hamburg Reference Centre (HRC; graded with the AFIP and Brandwein systems) and the other (n = 384) was derived from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW; graded with the AFIP system). The reliability of both the AFIP and Brandwein grading systems was excellent (n = 155). The weighted kappa for inter-rater agreement was 0.81 (95% CI 0.65-0.97) and 0.83 (95% CI 0.71-0.96) for the AFIP and Brandwein systems, respectively. The 5-year relative survival was 79.7% (95% CI 73.2-86.2%). Although the Brandwein system resulted in a higher rate of G3-MECs, survival in G3-tumors (AFIP or Brandwein grading) was markedly worse than in G1/G2-tumors. Survival in > T2 tumors was markedly worse than in those with lower T-stage. Also, fusion-negative MECs had a worse 5-year progression-free survival. The frequency of fusion-positive MECs in the HRC cohort was 78.4%, of which the majority (86.7%) was G1/G2-tumors. In conclusion, the AFIP and Brandwein systems are useful in estimating prognosis and to guide therapy for G3-MECs. However, their significance regarding young age (≤ 30 years) and location-dependent heterogeneity of in particular G2-tumors is more questionable. We conclude that CRTC1/3-MAML2 testing is a useful adjunct to histologic scoring of MECs and for pinpointing tumors with poor prognosis with higher precision, thus avoiding overtreatment.
2021-10-28 | ETV6-NTRK3-positive parotid mammary analogue secretory carcinoma: a case report.
Mammary analogue secretory carcinoma (MASC) is a recent discovered entity of salivary glands tumors, reported for first time in 2010. The presence of a translocation encodes the ETS variant transcription factor 6-neurotrophic tyrosine receptor kinase (ETV6-NTRK3) gene fusion differences MASC from other tumors. A 68-year-old male showed a non-painful right parotid enlargement, came from dermatology service, and followed by some facial squamous cell carcinomas. A computed tomography (CT) scan showed a 1.7×1.6 cm right parotid enlargement in superficial lobe. The patient underwent a right superficial parotidectomy. The final pathology confirmed the presence of ETV6-NTRK3-positive MASC. Complete right deep parotidectomy and functional cervical emptying were performed. It is necessary to establish an appropriated differential diagnosis between salivary gland tumors. MASC is a low-grade malignancy cancer that sometimes can evolve to a high-grade tumor that might produce local and distance dissemination. Most times, these tumors are only treated by surgical resection and evaluating by a multidisciplinary team the need of more treatments. In our case, the patient showed a primary parotid tumor, removed surgically with free edges, and being identified as MASC. We decided to underwent neck dissection and discovered a second MASC focus on cervical salivary gland; however, there was no nodal dissemination. The patient remains disease-free after 14 months from last surgery. It is important to keep studying genetic therapy targets to ETV6-NTRK3 to obtain a new therapy line to treat those cases that require.
2019-11-15 | Novel gene fusions in secretory carcinoma of the salivary glands: enlarging the ETV6 family.
Secretory carcinoma (SC) of the salivary gland is a low-grade malignancy associated with a well-defined clinical, histologic, immunohistochemical, and cytogenetic signature. Although the t(12;15) (p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion is well documented, advances in molecular profiling in salivary gland tumors have led to the discovery of RET as another ETV6 gene fusion partner in SC. Here, we applied an RNA-based next-generation sequencing (NGS) approach for fusion detection on 14 presumed SC. The cases included 7 SC with classic ETV6-NTRK3 gene fusion and 3 SC harboring ETV6-RET gene fusion. In addition, 2 cases revealed a NCOA4-RET gene fusion and were subsequently reclassified as intraductal carcinomas. One case with an unusual dual-pattern morphology revealed a novel translocation involving ETV6, NTRK3, and MAML3 gene rearrangements. Interestingly, no ETV6-NTRK3 or ETV6-RET SC was ever documented to have this unique dual-pattern morphology or harbor a MAML3 mutation. The remaining case had no detected chromosomal abnormalities. Advances in molecular profiling of SC have led to the discovery of novel fusion partners such as RET and now MAML3. Further molecular characterization of salivary gland neoplasms is needed as these mutations may present alternative therapeutic targets in patients with these tumors.
2016-10-12 | Type III TGF-β receptor inhibits cell proliferation and migration in salivary glands adenoid cystic carcinoma by suppressing NF-κB signaling.
It is known that the TGF-β superfamily receptors act as master regulators of cancer progression. However, alteration and role of type III TGF-β receptor (TβRIII, or betaglycan) as the most abundant of the TGF-β receptor has not been explored in salivary gland adenoid cystic carcinoma (ACC). Here, we reported that tumor biopsies and matched normal human salivary glands from patients with ACC were examined for the expression of TβRIII. The expression of TβRIII protein is significantly decreased in ACC patients based on immunohistochemistry and western blot analysis. In vitro, a transient overexpression of TβRIII markedly induced apoptosis and cell cycle arrest in the G2/M phase, thereby inhibited cell viability and migration of ACC-M cells. Co-immunoprecipitation revealed that TβRIII, scaffolding protein-arrestin2 (β-arrestin2) and IκBα formed a complex. Transient overexpression of TβRIII decreased p-p65 expression and increased IκBα expression, which was abolished by knockdown of β-arrestin2. The present study defines TβRIII as a biomarker exerting antitumor action on ACC progression.Gene therapy of TβRIII may be a powerful new approach for ACC disease.
oligonucleotides
2026-02-02 | NDC80 kinetochore complex component is a potential molecular target of adenoid cystic carcinoma.
Adenoid cystic carcinoma (ACC) is a slow-growing malignant tumour that primarily originates from the major and minor salivary glands. The relationship between the NDC80 kinetochore complex component (NUF2) and ACC remains to be elucidated. The present study obtained gene expression information from the Gene Expression Omnibus database (GSE88804 and GSE153002). Differentially expressed genes were identified by using the 'limma' package in R. A protein-protein interaction network was constructed with the Search Tool for Retrieval of Interacting Genes/Proteins database and key genes were extracted using Cytoscape software. Analysis of differential expression levels of hub genes in tumour and normal tissue was performed using Tumour Immune Estimation Resource (TIMER) and GSE36820 profiles. Gene Ontology enrichment was subsequently analysed based on differences in NUF2 expression in tumour tissues. In addition, single sample Gene Set Enrichment Analysis (ssGSEA) was used for the quantitative analysis of immune cell infiltration in ACC. Western blotting and immunohistochemistry were used to assess NUF2 expression levels in tumour and adjacent non-tumour tissues. Small interfering RNA (siRNA) was used to decrease NUF2 expression in ACC cell lines. The biological functions of NUF2 were analysed using Cell Counting Kit-8 and wound healing assays. A total of 248 differential genes were identified by differential expression analyses, with 113 genes upregulated and 135 downregulated. A total of 7 hub genes, namely, CDK1, budding uninhibited by benzimidazoles 1 mitotic checkpoint serine/threonine kinase B, DNA topoisomerase II α, cyclin B2, NUF2, budding uninhibited by benzimidazoles 1 and centromere protein F, were obtained using the 'cytoHubba' plugin. The TIMER, standardized and GSE36820 databases revealed that the expression levels of NUF2 were higher in ACC tissues compared with normal tissue samples. Western blotting and immunohistochemical staining of ACC tissues provided evidence of NUF2 upregulation in ACC tissue compared with normal tissue. NUF2-related genes were enriched in 'ameboidal-type cell migration', 'collagen-containing extracellular matrix' and 'actin binding'. ssGSEA analysis revealed that the expression level of NUF2 was notably associated with activated CD4+ T cells, memory B cell and plasmacytoid dendritic cell. ACC cells transfected with NUF2 siRNA exhibited decreased proliferation and migration compared with the control. In conclusion, NUF2 is upregulated in ACC and is associated with immune cell infiltration. Functional studies demonstrated that NUF2 promotes ACC cell proliferation and migration, suggesting its potential as a therapeutic target for ACC.
2024-02-26 | Dynamic Role of miRNAs in Salivary Gland Carcinomas: From Biomarkers to Therapeutic Targets.
Salivary gland carcinomas (SGCs) are a rare group of malignant neoplasms of the head and neck region. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been associated with the control biological process and oncogenic mechanism by the regulation of gene expression at the post-transcriptional level. Recent evidence has suggested that miRNA expression may play a role in the tumorigenesis and carcinogenesis process in SGCs. This review provides a comprehensive literature review of the role of miRNAs expression in SGCs focusing on the diagnostic, prognostic, and therapeutic applications. In this review, numerous dysregulated miRNAs have demonstrated an oncogenic and suppressor role in SGCs. In the future, these miRNAs may eventually constitute useful diagnostic and prognostic biomarkers that may lead to a better understanding of SGCs oncogenesis. Additionally, the development of therapeutic agents based on miRNAs may be a promising target in SGC treatment.
2023-05-12 | Single-cell RNA sequencing reveals the heterogeneity and microenvironment in one adenoid cystic carcinoma sample.
Adenoid cystic carcinoma (ACC) is one of the most common malignancy of the major salivary glands with a high recurrence rate and poor prognosis. Determining tumor heterogeneity and factors in the microenvironment may provide novel therapeutic targets for ACC. We performed single-cell RNA sequencing of one ACC sample and normal salivary gland tissues from a patient to analyze tumor heterogeneity, immunosuppressive landscape, and intercellular communication networks. The heterogeneity of epithelial cells in ACC tissues was significantly higher compared with that in normal tissues, whereas immune cells were almost absent. We found four malignant cell clusters in ACC and explored their characteristics and function. In tumor tissues, CD8 + cytotoxic T cells and CD4 + T helper cells were significantly decreased, whereas IgA + plasma cells were absent. There were two clusters of macrophages, one representing IL1B macrophages and the other consisted of a cluster of macrophages associated with the epithelial mesenchymal transition (EMT). Both were significantly different from the normal tissue composition. In addition, the communication between epithelial cells and other cells in the tumor tissue was enhanced. MIF-CD74 and APP-CD74 were significantly upregulated. We comprehensively described the heterogeneity of ACC and the tumor microenvironment (TME) from a single cell perspective including cell characteristics, immune cell infiltration, and cell communication. CLINICAL RELEVANCE: This study provided further insights into ACC and may lead to new treatment strategies.
2022-12-23 | Overexpression of LAG3, TIM3, and A2aR in adenoid cystic carcinoma and mucoepidermoid carcinoma.
Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the two most frequent malignancies of salivary glands. This study aims to explore the expression and migration of LAG3, TIM3, and A2aR in AdCC and MEC, and the potential relationship with oncogenic signaling molecules and immunosuppressive cytokines. Custom made human salivary gland tissue microarrays included 81 AdCCs, 52 MECs, 76 normal salivary glands (NSG), and 14 pleomorphic adenoma (PMA) samples. Immunohistochemical analysis of lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), adenosine 2a receptor (A2aR), oncogenic phosphorylated S6 kinase (p-S6) and ERK1/2 (p-ERK1/2 ), and TGF-β1 was performed with salivary gland tissue microarrays of human samples. The correlation of the immunostaining was analyzed based on a digital pathological system, and data were evaluated by hierarchical cluster. Further in vitro studies of knockdown immune checkpoints LAG3, TIM3, and A2aR were carried out by siRNA transfection. The expression levels of LAG3, TIM3, and A2aR were remarkably increased in AdCC and MEC, compared with NSG and PMA samples, but were independent of pathology grade. They were closely correlated with TGF-β1, slightly related to p-ERK1/2 and p-S6. After the knockdown of immune checkpoints LAG3, TIM3, and A2aR, the migration of SACC-LM cell line was significantly reduced. These results suggested that LAG3, TIM3, and A2aR are overexpressed in AdCC and MEC, may promote migration of SACC-LM cell and correlated with TGF-β1 and oncogenic signaling pathways.
2021-02-04 | Metallothionein Expression and its Influence on the In Vitro Biological Behavior of Mucoepidermoid Carcinoma.
Mucoepidermoid carcinoma (MEC) is the most common tumor in the salivary glands, often presenting with recurrence and metastasis due to its high invasive capacity. Metallothionein (MT), a zinc storage protein that supplies this element for protease activity, is probably related to mucoepidermoid carcinoma behavior. This prompted us to characterize a cell line derived from mucoepidermoid carcinoma and to correlate metallothionein expression with transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α) and matrix metalloproteinases (MMPs). Transcriptomic analysis and cytogenetic assays were performed to detect the expression of genes of interest and cellular chromosomal alterations, respectively. MEC cells with a depleted metallothionein 2A (MT2A) gene were subjected to Western blot to correlate metallothionein expression with growth factors and MMPs. Additionally, cells with depleted MT were subjected to migration and invasion assays. The transcriptomic study revealed reads mapped to cytokeratins 19 and AE1/AE3, α-smooth muscle actin, vimentin, and fibronectin. Cytogenetic evaluation demonstrated structural and numerical alterations, including the translocation t(11;19)(q21;p13), characteristic of MEC. Metallothionein depletion was correlated with the decreased expression of TGF-α and MMP-9, while TNF-α protein levels were augmented. Migration and invasion activity were diminished after metallothionein silencing. Our findings suggest an important role of MT in MEC invasion, through the regulation of proteins involved in this process.
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2025-10-01 | Construction And Molecular Characterization Of Rare Salivary Gland Tumor Organoids
To establish a personalized research model for rare subtypes of salivary gland tumor, bridging foundational investigations and clinical applications to advance precision oncology in this understudied field. Sample Collection Rare salivary gland tumor tissuescollected under sterile protocols. Ethics: Approved by IRB of China Medical University Hospital of Stomatology (#2025010). Clinical Data Integration Statistical analysis of clinical metadata and organoid parameters. Organoid Histological Evaluation Assessment: Inverted microscopy, H&E/immunofluorescence staining (lineage-specific markers). Morphometric/molecular comparisons to parental tumors using non-parametric tests. Transcriptomic Profiling RNA-seq: Tumor tissues, normal glands, and organoids. Bioinformatics: Dimensionality reduction, consensus clustering (Consensus Cluster Plus), differential expression (DESeq2). 1.Organoid models for six rare salivary gland tumor subtypes—including two benign (myoepithelioma [ME] and canalicular adenoma [CA]) and four malignant (epithelial-myoepithelial carcinoma [EMC], myoepithelial carcinoma [MC], secretory carcinoma [SC], and nonspecific adenocarcinoma [NOS])—were successfully established alongside normal gland organoid controls, demonstrating rapid maturation by day 14 and growth plateauing at day 21. 2.Organoids derived from myoepithelial-dominant tumors (ME, MC) showed reduced proliferation efficiency, while others exhibited robust expansion. 3.These organoids faithfully retained parental tumor morphology, transcriptional profiles and cellular heterogeneity mirroring diagnostic and structural features of original tumors. Salivary gland tumor organoids serve as high-fidelity in vitro models for studying rare salivary gland tumors, effectively recapitulating the morphological and molecular characteristics of their parental tumors offering a powerful platform to advance personalized therapeutic strategies and mechanistic studies for rare salivary gland carcinomas.
2025-04-17 | Integrative genomic pan-cancer analysis reveals the prognostic significance of DEFB1 in tumors.
Defensin beta 1 (DEFB1) is a key immune response gene, but its role in cancer remains unclear. This study aims to explore DEFB1 expression, genetic alterations, immune infiltration, and prognostic significance across various cancer types. We analyzed DEFB1 expression and its association with cancer prognosis using data from public platforms, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA). Additionally, we examined DEFB1 genetic alterations, immune cell infiltration, and its molecular partners using various bioinformatics tools. DEFB1 expression was highest in salivary glands, kidneys, and pancreas. In cancers, DEFB1 was upregulated in cholangiocarcinoma, kidney chromophobe, and melanoma, but downregulated in breast, colon, and rectal cancers. High DEFB1 expression was linked to poorer overall survival in lung adenocarcinoma and pancreatic adenocarcinoma, but better survival in head and neck squamous cell carcinoma. Genetic analysis revealed alterations in liver and gastric cancers. Immune infiltration analysis showed a correlation between DEFB1 and cancer-associated fibroblasts in liver cancer, while neutrophil infiltration was linked to bladder carcinoma, diffuse large B-cell lymphoma, and lung squamous cell carcinoma. Key genes associated with DEFB1 included KLK1, BSND, and CLCNKB. This study highlights DEFB1's potential as a prognostic biomarker and its influence on the tumor immune microenvironment across different cancers. These findings suggest DEFB1 could be a target for future cancer therapies, although further studies are needed to validate these results.
2024-09-07 | Functional reconstruction of tissue defects after total parotidectomy using a modified submandibular gland flap.
Reconstruction of soft tissue defects after total parotidectomy requires a feasible and effective pedicled flap with sufficient volume. In this study, we introduce a modified submandibular gland flap (SMGF) for functional reconstruction of soft tissue defects resulting from total parotidectomy. This study included 12 patients diagnosed with parotid gland carcinoma undergoing total parotidectomy and ipsilateral selective neck dissection. The modified SMGF was harvested and transferred to the parotid bed. This procedure was coupled with anastomosis between the parotid gland duct and Wharton's duct. The feasibility of the surgery, postoperative complications, facial profile restoration, and salivary secretion were assessed. All SMGFs pedicled only over the proximal facial artery survived without major complications. Facial profiles were well-restored, and salivary secretion was partially reserved. During the postoperative follow-up, no tumor recurrence was observed in any of the cases, and the volume of the SMGFs did not show obvious atrophy. The modified SMGF is a viable solution for volume restoration and functional reconstruction after total parotidectomy. This modified technique is simple and feasible for the functional reconstruction of soft tissue defects after total parotidectomy compared to other flaps and is worthy of clinical promotion.
2024-08-29 | Establishment and characterization of cMYB-expressing human salivary adenoid cystic carcinoma cell lines (UM-HACC-14, UM-HACC-6) and matching patient-derived xenograft model (UM-PDX-HACC-14).
Limited availability of authentic human adenoid cystic carcinoma (ACC) cell lines has hindered progress in understanding mechanisms underpinning the biology of this disease and the development of safe and effective therapies. Surgical human ACC specimens (UM-HACC-6, UM-HACC-14) were dissociated into single cell suspensions and cultured in fibronectin-coated flasks. Alternatively, tumor fragments were transplanted subcutaneously into female immunodeficient (SCID) mice to establish patient-derived xenograft tumors (PDX; UM-PDX-HACC-14). Both ACC cell lines showed continuous growth in monolayers for over 100 passages. Total RNA-Seq, RT-PCR, and FISH analysis revealed that both are MYB-NFIB fusion negative. Western blots revealed passage-dependent expression of E-Cadherin, PCNA, p63, phospho-c-MYB, and NFIB. Both, UM-HACC-14 and UM-HACC-6 cells exhibited tumorigenic potential when injected orthotopically into mouse submandibular glands. UM-HACC-14, patient-matching UM-PDX-HACC-14, and the UM-HACC-6 cell line are new, authenticated preclinical models of ACC that are well suited for mechanistic and developmental therapeutics studies.
2023-11-16 | Identifying potential immuno-oncology targets in salivary gland mucoepidermoid carcinoma based on inflammatory status and treatment response.
Mucoepidermoid carcinoma is a rare salivary gland malignant tumour. This study aimed to investigate inflammatory and immune signatures of mucoepidermoid carcinoma by identifying potential proteo-transcriptomic biomarkers towards the development of precision immuno-oncology treatment strategies. A total of 30 biopsies obtained from patients diagnosed with mucoepidermoid carcinoma between 2013 and 2022 were analysed after H&E staining for scoring of histological inflammatory stroma subtypes and inflammatory hotspots with QuPath. Multiplex immunofluorescence staining and NanoString nCounter PanCancer IO 360™ panel were used to assess stroma and tumour inflammation signatures in high grade mucoepidermoid carcinoma cases in the tumour microenvironment via proteomics and transcriptomics, respectively. Inflammatory cells within the histological inflammatory stroma inflammatory (HIS-INF/hot) tumour neighbourhoods were greater compared to the histological inflammatory stroma-immune desert (HIS-ID/cold) (p = 0.001). A similar trend was observed between treatment non-responders and responders in stroma neighbourhoods (p = 0.0625) and in stroma-to-interface inflammatory hotspots (p = 0.0081), indicating an augmented inflammatory response in hot tumours and non-responders. Furthermore, there were striking differences in the expression of pan-immune leukocyte marker CD45 between responders and non responders particularly in the tumour neighbourhoods (p = 0.0341), but such were not robust for PD-1 and macrophage fractions. Additionally, transcriptomic analysis revealed key differences in leukocyte activation profiles between responders and non-responders. This preliminary report unveils the importance of assessing immune leukocyte cellular fractions and pathways for future prognostic biomarker discoveries in mucoepidermoid carcinoma as per the involvement of CD45-driven inflammatory and immune mediators in high grade mucoepidermoid carcinoma in non-responders to treatment. These findings will potentially contribute to the development of novel personalised immunotherapies.
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Drug Discovery Landscape
1 orphan drug designation for Malignant epithelial tumor of salivary glands.
1 orphan drug designation for Malignant epithelial tumor of salivary glands.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Larotrectinib sulfate [Vitrakvi] | small molecules | EMA | Bayer AG |
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