Ocular surface squamous neoplasia: Update on genetics, epigenetics and opportunities for targeted therapy

The purpose of this review is to explore the molecular foundations of ocular surface squamous neoplasia (OSSN), focusing on the genetic and epigenetic aspects. While current management strategies include surgical excision and medical therapies, the understanding of OSSN's molecular basis remains limited, hindering the development of targeted treatments.

A comprehensive MEDLINE search was conducted for literature published between January 1993 and October 2023. Only studies with original data on molecular, genetic, or epigenetic mechanisms, such as mutations, gene expression, and genetic predispositions were included. Articles were excluded if they focused solely on clinical management without addressing these factors, or if they were reviews, editorials, or opinion pieces.

The search yielded a total of 108 articles, out of which 39 articles met the criteria for further analysis. Investigations into OSSN have identified key DNA mutations in the TP53, HGF, EGFR, TERT, and CDKN2A genes, indicating common oncogenic pathways shared with other squamous cell carcinomas (SCCs). Significant epigenetic changes were identified, including DNA methylation, histone modifications, and altered miRNA expression patterns. Epigenetic dysregulation of critical tumor suppressors and oncoproteins, further highlight the complex genetic landscape of OSSN.

The molecular alterations identified in OSSN not only enhance our understanding of its biology but also have potential as novel biomarkers for early detection, prognostic evaluation, and as therapeutic targets. The identification of genetic and epigenetic markers in OSSN signifies progress towards personalized medicine approaches. Further studies and collaborative efforts are essential to validate these molecular markers and translate them into clinical practice, potentially revolutionizing OSSN management and improving patient outcomes.