Diagnostic and therapeutic implications of new molecular biomarkers in salivary gland cancers

Abstract

Salivary gland carcinomas (SGCs) are uncommon tumors, constituting approximately 5% of all cancers of the head and neck. They are a heterogeneous group of diseases that pose significant diagnostic and therapeutic challenges. The treatment of patients with SGCs is mainly restricted to surgery and/or radiation therapy and there is only limited data available on the role of conventional systemic and targeted therapies in the management of patients with advanced disease. There is thus a great need to develop new molecular biomarkers to improve the diagnosis, prognostication, and therapeutic options for these patients. In this review, we will discuss the most recent developments in this field, with focus on pathognomonic gene fusions and other driver mutations of clinical significance. Comprehensive cytogenetic and molecular genetic analyses of SGCs have revealed a translocation-generated network of fusion oncogenes. The molecular targets of these fusions are transcription factors, transcriptional coactivators, and tyrosine kinase receptors. Prominent examples of clinically significant fusions are the MYB-NFIB fusion in adenoid cystic carcinoma and the CRTC1-MAML2 fusion in mucoepidermoid carcinoma. The fusions are key events in the molecular pathogenesis of these tumor types and contribute as new diagnostic, prognostic, and therapeutic biomarkers. Moreover, next-generation sequencing analysis of SGCs have revealed new druggable driver mutations, pinpointing alternative therapeutic options for subsets of patients. Continued molecular characterization of these fusions and their down-stream targets will ultimately lead to the identification of novel driver genes in SGCs and will form the basis for development of new therapeutic strategies for these patients.

Keywords: Biomarker; Chromosome translocation; Gene fusion; Mutation; Oncogene; Salivary gland cancer; Therapeutic target.