Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Abstract

Background: Adenoid cystic carcinoma (ACC) is a rare tumor of secretory glands. In this study, recent advances in molecular characterization and in therapeutics are reviewed.

Methods: A search of articles in PubMed and of abstracts from national meetings was performed regarding ACC.

Results: Recent genetic analyses found that recurrent chromosome 6:9 translocations in ACC generate an MYB:NFIB gene fusion resulting in overexpression of the MYB oncoprotein. Several other frequent mutations are recently published that may be relevant for drug development. Several trials of targeted drugs are reviewed. Some agents delay tumor progression, but tumor responses remain rare.

Conclusion: ACCs have a characteristic chromosomal translocation, but also frequently pick up additional mutations. Clinical research is limited by the rarity and slow growth of ACC. Several ongoing trials are testing agents that inhibit fibroblast growth factor receptor signaling or other signaling pathways. Novel treatments based on the recently sequenced tumor genome are under development.

Keywords: MYB gene; NFIB gene; adenoid cystic carcinoma; nuclear factor I/B; salivary gland; tyrosine kinase inhibitor.

Figure 1

(A) The photomicrograph shows a typical adenoid cystic carcinoma (ACC) with cribriform features. The tumor is arranged in nests of cells, with many nests containing cyst‐like spaces with abundant extracellular matrix. The color of the matrix varies from pale red to light blue. In the inset, the tumor cells are shown to have scant cytoplasm and nuclei that show minimal pleomorphism. The tumor cell nuclei have small to inconspicuous nucleoli and the chromatin is finely dispersed. Mitotic figures are rare. (Hematoxylin‐eosin stain, original magnification ×100, inset ×400.) (B) The photomicrograph shows an adenoid cystic carcinoma in an immunohistochemical stain for the MYB protein. Protein location is visualized as brown staining. The majority of tumor cells show moderate to strong staining, with localization to the nuclei (diaminobenzidine immunohistochemical stain, original magnification ×400). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Tumor response in a patient with adenoid cystic carcinoma (ACC) treated for 2 months with the tyrosine kinase inhibitor, dovitinib 500 mg. The fused positron emission tomography–CT images were obtained on a participant in a clinical trial with untreated primary salivary gland ACC. The baseline scan is shown on the left and the 2‐month follow‐up scan is on the right. The standardized fluorodeoxyglucose uptake in the right posterior maxilla is markedly decreased in the absence of any surgical or other intervention. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com]