Adenoid Cystic Carcinoma of the Lacrimal Gland: Clinical, Genetic and Molecular Characteristics

Lacrimal Gland Adenoid Cystic Carcinoma (LGACC) is a rare but devastating cancer with a high modality rate. In 75% of cases, perineural migration of LGACC can spread intracranially and invade into orbital bone. Currently, patients with LGACC are treated with chemotherapy and exenteration. Despite these interventions, LGACC has a high frequency of local recurrence and distant metastasis. Only 50% of patients survive to 5 years after diagnosis, and just 25% survive to 15 years. To overcome the difficulties in preventing cancer recurrence and metastasis, better treatments for LGACC are urgently needed. To better understand the pathophysiology of LGACC, we have reviewed the recent literature on clinical and research advances in LGACC. In this chapter, we mainly focus on the genetic and mechanistic studies on important tumorigenic signaling molecules such as MYB, Notch and FGFR. MYB is a proto-oncogene and key regulator of stem cells. In LGACC, MYB-NFIB fusion transcripts are formed by chromatin rearrangements in the MYB locus, leading to the overexpression of MYB. Mutations in the PEST domain and heterodimerization domain of Notch cause accumulation of the Notch intracellular domain (NICD), which is the biologically active form of Notch. The fibroblast growth factor receptor pathway also plays an important role during lacrimal gland development. Growing evidence indicates that FGFR is an effective biological target in other types of ACC. Small molecule inhibitors for FGFR may therefore shed new light on the treatment of LGACC.