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PubMed2026

Efficacy of S-1 Monotherapy for Salivary Duct Carcinoma With MYC Amplification.

BACKGROUND/AIM: 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. CASE REPORT: 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. CONCLUSION: 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.

Humans↗
PubMed2026

Salivary duct carcinoma- contemporary nuts and bolts from pathologist perspective.

INTRODUCTION: Salivary gland carcinomas are highly heterogeneous malignancies that present a complex variety of histological features and distinct clinical behaviors, with salivary duct carcinoma (SDCa) as the most clinically severe and aggressive subtype. The standard of care for these patients is a combined approach of surgery followed by radiotherapy. The aggressive clinical course of SDCa is primarily driven by frequent disease recurrences and systemic spread. AREAS COVERED: The publication of WHO 5th Classification of Head and Neck tumors has sparked a surge in research targeting SDCa. Owing to the highly aggressive behavior of the tumor, most literature heavily emphasizes the molecular pathology of SDCa.A systematic literature search was conducted using the PubMed with the following search terms: salivary duct carcinoma AND pathology OR updates OR molecular OR signaling pathway OR gene expression OR mutation OR oncogene OR tumor suppressor OR DNA methylation OR tumor microenvironment. Results were limited to primary research articles in English language. EXPERT OPINION: This article outlines key advancements in SDCa morphology, molecular pathology, and targeted therapies. Patient management in precision oncology will be fundamentally transformed by the classification of new morphologic subtypes, the discovery of molecular biomarkers, and an enhanced comprehension of tumor microenvironment.

HER 2↗
PubMed2026

Human Epidermal Growth Factor Receptor-2 positive metastatic salivary duct carcinoma with remarkable response to targeted therapy: a case report and therapeutic implications.

Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy that frequently overexpresses Human Epidermal Growth Factor Receptor 2 (HER2). Despite the increasing recognition of HER2-targeted strategies, evidence remains limited and largely derived from small trials and case series. We report the case of a middle-aged man with HER2-positive metastatic SDC who achieved near-complete pathologic and radiological response to trastuzumab and docetaxel, enabling surgical resection for locoregional control. This case highlights the role of anti-HER2 therapy as a first-line strategy in SDC and underscores the importance of individualized management plans integrating systemic treatment and locoregional measures.

Humans↗
PubMed2026

Molecular characterization of salivary cancers: Patterns of genomic alterations and potential for impact on therapeutic choices.

BACKGROUND: Salivary cancers are rare malignancies with diverse histologies, molecular landscape, and limited effective systemic therapy options. Recent tumour genomics research has identified driver alterations in salivary gland cancers that have led to personalized therapy approaches. The primary objective was to perform molecular characterization using next generation sequencing (NGS) panel and evaluate the potential impact of results on clinical decision-making and treatment outcomes. METHODS: Patients with locally advanced or incurable metastatic salivary cancers suitable for systemic therapy underwent NGS tumour testing with an amplicon-based DNA/RNA NGS panel. Patient demographics, baseline characteristics, treatment and treatment outcomes were retrospectively collected. RESULTS: From 2021 to 2024, 58 advanced salivary cancer patients underwent molecular characterization of their tumour. Baseline characteristics at diagnosis: male 60%, median age 67, most common histologies; adenoid cystic 27%, salivary duct 19% and mucoepidermoid 12%. PIK3CA alterations were the most common molecular finding across all subtypes 22% (13/58) and were enriched in salivary duct carcinoma 73% (8/11). Other alterations identified were: ERBB2 (4), EGFR (2), HRAS (3), NTRK3 (2), BRAF p.V600E (1), and RET (1). Immunohistochemistry identified androgen receptor positivity across salivary cancer subtypes in 8/19 and HER2 positivity in 2/20 tested. Twenty-two patients received systemic therapy prior to NGS results for incurable/metastatic disease, first line treatments included 69% chemotherapy, 18% anti-androgen, 9% lenvatinib, 4% trial. CONCLUSION: Molecular characterization of salivary cancers identified targetable alterations in 37% of patients. The identification of potential therapeutic targets offers the opportunity for expanded treatment options to benefit salivary gland cancer patients.

Metastatic salivary gland cancer↗