Salivary glands adenoid cystic carcinoma: a molecular profile update and potential implications

Abstract

Adenoid cystic carcinoma (ACC) is an aggressive tumor with a high propensity for distant metastasis and perineural invasion. This tumor is more commonly found in regions of the head and neck, mainly the salivary glands. In general, the primary treatment modality for ACC is surgical resection and, in some cases, postoperative radiotherapy. However, no effective systemic treatment is available for patients with advanced disease. Furthermore, this tumor type is characterized by recurrent molecular alterations, especially rearrangements involving the MYB, MYBL1, and NFIB genes. In addition, they also reported copy number alterations (CNAs) that impact genes. One of them is C-KIT, mutations that affect signaling pathways such as NOTCH, PI3KCA, and PTEN, as well as alterations in chromatin remodeling genes. The identification of new molecular targets enables the development of specific therapies. Despite ongoing investigations into immunotherapy, tyrosine kinase inhibitors, and anti-angiogenics, no systemic therapy is approved by the FDA for ACC. In this review, we report the genetic and cytogenetic findings on head and neck ACC, highlighting possible targets for therapeutic interventions.

Keywords: MYB; adenoid cystic carcinoma; molecular profile; oral cancer; target therapies.

Figure 1

(A) Main gene fusions of MYB gene. (B) Main gene fusions of MYBL1 gene. (C) Gene fusion of MYB with the super enhancers including YTHDF3, RAD51B; (D) Alteration on regulation of MYB expression: in normal conditions the MYB is downregulated by miR-15a/16 or miR-150, however in ACC tumor occur the deletion of 3’ UTR region blocking the ligation of their miRNA, which facilities the overexpression of MYB gene.

Figure 2

Main therapeutic targets to ACC tumor and their respective therapies. ATRA, all-trans retinoic acid; EGFR, epidermal growth factor receptor; IGFR1, insulin like growth factor 1 receptor; VEGFR, vascular endothelial growth factor; HDAC, Histone deacetylase. Created with BioRender.com.