Novel therapeutic strategies for malignant salivary gland tumors: lessons learned from breast cancer

Abstract

Malignant salivary gland tumors (MSGTs) account for 2-6% of all head and neck cancers. Despite the rarity, MSGTs have been of great interest due to a wide variety of pathological features and high metastasis rates resulting in poor prognosis. Surgical resection followed by radiation therapy represents the main treatment of this malignancy. Adjuvant therapy is reserved for the management of local recurrence, no longer amenable to additional local therapy, and for metastasis. Based on the studies from other types of tumors, particularly breast cancer, the expression and function of sex steroid hormone receptors in cancer have been extensively studied and applied to diagnosis and treatment. Although a number of studies in MSGTs have been published, the rationale for hormone therapy is still controversial due to the disparate results and insufficient number of cases. However, some recent reports have demonstrated that certain salivary gland neoplasms are similar to breast cancer, not only in terms of the pathological features, but also at the molecular level. Here, we shed light on the biological similarity between MSGTs and certain types of breast cancer, and describe the potential use of hormone and additional therapies for MSGTs.

Figure 1

Histological comparison of malignant salivary and mammary gland tumors. Salivary glands and mammary glands are both tubuloacinar exocrine tissues sharing similar morphological features. It is, therefore, expected that the tumors originating from these two different glands would show similarities in their response to hormonal treatment.

Figure 2

Pg suppresses proliferation and invasion of both salivary gland and breast cancer cells. In our recent studies, the inhibitory effect of Pg on the proliferative and invasive activities of the salivary gland and breast tumor cells was demonstrated, suggesting some common mechanisms. In both types of cancers, expression of Id-1 and c-myc was downregulated after Pg treatment, whereas p21 expression level was upregulated.