A Review of the Molecular Landscape of Adenoid Cystic Carcinoma of the Lacrimal Gland

Abstract

Adenoid cystic carcinoma (ACC) has a worldwide incidence of three to four cases per million population. Although more cases occur in the minor and major salivary glands, it is the most common lacrimal gland malignancy. ACC has a low-grade, indolent histological appearance, but is relentlessly progressive over time and has a strong proclivity to recur and/or metastasise. Current treatment options are limited to complete surgical excision and adjuvant radiotherapy. Intra-arterial systemic therapy is a recent innovation. Recurrent/metastatic disease is common due to perineural invasion, and it is largely untreatable as it is refractory to conventional chemotherapeutic agents. Given the rarity of this tumour, the molecular mechanisms that govern disease pathogenesis are poorly understood. There is an unmet, critical need to develop effective, personalised targeted therapies for the treatment of ACC in order to reduce morbidity and mortality associated with the disease. This review details the evidence relating to the molecular underpinnings of ACC of the lacrimal gland, including the MYB–NFIB chromosomal translocations, Notch-signalling pathway aberrations, DNA damage repair gene mutations and epigenetic modifications.

Translational Insights in the Landscape of Salivary Gland Cancers: Ready for a New Era?

“…Genes regulated by MYB include proteins able to accelerate the cell cycle such as CCNA1, CCNB1, CCNE1, and CCND1, as well as others involved in inhibiting apoptosis induction such as API5, BCL2, BIRC3. MYB is also able to increase the transcription of genes involved in angiogenesis, such as FGF2, KIT, MYC, VEGFA, and cell migration (ICAM1, MMP7, and MMP9) [ 21 ]. Figure 2 shows the intracellular pathway stimulated by MYB-NFIB chimeric enzyme, illustrating some of the possible ways to promote carcinogenesis.…”