Unraveling the molecular basis of salivary gland cancer: recent progress, diagnostic, prognostic, and therapeutic implications – a narrative review, part I

PURPOSE: Salivary gland cancers are rare and heterogeneous malignancies. In recent years, an increasing number of molecular alterations have been identified across the different histological subtypes, leading to the recognition of new entities and refinement of the tumor classification. These molecular alterations are also becoming essential in the diagnostic workup and may carry both prognostic and therapeutic significance. Furthermore, the characterization of these is fundamental for understanding current targeted therapies as well as for the development of new treatments. METHODS: An extensive review of the literature from the last 15 years was conducted, with a specific focus on molecular alterations and targeted therapies in the following salivary gland carcinomas: mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, and secretory carcinoma. RESULTS: We provide an updated overview of recurrent and/or specific molecular alterations for each histological subtype and summarize current knowledge regarding their mechanisms of tumorigenesis. Their diagnostic and prognostic implications are also discussed, and existing as well as emerging targeted therapies are reviewed. CONCLUSION: Knowledge of molecular alterations in salivary gland cancers not only enables more precise classification and diagnosis but also contributes to improved prognostic stratification and the development of targeted therapies. It provides the foundation for development of personalized treatment approaches to the most common salivary gland carcinomas.