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.

PTEN Deregulation Mechanisms in Salivary Gland Carcinomas

“…In conclusion, PTEN suppressor gene silencing plays a critical role in SGCs by enhancing signal transduction to the nucleus. Mechanisms of this deregulation include different point mutations and deletions of this specific gene locus that demonstrate in different SGC histo-types (55). PTEN silencing enhances PI3K/AKT/mTOR overactivation in pre-and malignant salivary gland epithelia.…”

Molecular Biology and Therapeutic Targets of Primitive Tracheal Tumors: Focus on Tumors Derived by Salivary Glands and Squamous Cell Carcinoma

“…Several tyrosine kinase receptors and growth factors are overexpressed in ACC. One of them is c-KIT, whose mutations affect signaling pathways such as NOTCH, PI3K Catalytic Subunit Alpha, and PTEN, as well as alterations in chromatin remodeling genes [35]. c-Kit is a receptor tyrosine kinase whose dysregulate function caused by either overexpression or mutation is involved in the development of several cancers such as hematological malignancies, thyroid cancer and breast cancer [36].…”