[Advances in the molecular pathogenesis of lacrimal gland adenoid cystic carcinoma and associated targeted therapies].

Abstract

Lacrimal gland adenoid cystic carcinoma (LGACC), the most prevalent malignant epithelial tumor of the lacrimal gland, exhibits high invasiveness and poor prognosis. Despite aggressive local therapies, the 5-year and 10-year survival rates remain at 50% and 20% respectively. This review comprehensively synthesizes histopathological features, molecular mechanisms, and therapeutic advances in LGACC. Histopathological analysis highlights three classical subtypes (tubular, cribriform, and solid) with distinct prognostic implications, particularly emphasizing the detrimental survival impact of tumors undergoing high-grade transformation. At the molecular level, in-depth elucidation reveals the pivotal roles of NOTCH pathway mutations and MYB overexpression in driving oncogenesis through hyperactivation of receptor tyrosine kinase, PIP3/AKT, and ATR/BRCA signaling cascades. Current evidence demonstrates persistent therapeutic challenges: expanded surgical resection fails to significantly improve survival outcomes, while local excision combined with adjuvant therapies still faces substantial recurrence (80% at 5 years) and metastasis rates (66.9%). Emerging breakthroughs in targeted therapies warrant attention, including antisense oligonucleotides targeting MYB-NFIB fusion genes, clinical trial data of NOTCH inhibitors (e.g., AL101), and PARP inhibitor-based combinatorial regimens leveraging DNA damage repair mechanisms. By integrating fundamental research and clinical translational evidence, this review provides a theoretical framework for optimizing LGACC diagnosis and treatment paradigms.