Epigenetic aberrations and targeted epigenetic therapy of esophageal cancer.

Squamous cell carcinoma of the esophagus is one of the ten most frequent malignancies worldwide, characterized by a striking geographic variation in incidence. In North America and Europe, there has recently been a marked change in the epidemiology of this disease, where incidence rates for primary esophageal adenocarcinoma have increased in excess of any other human solid tumor. Although the reasons for this are largely unknown, several molecular genetic alterations have been associated with esophageal tumor progression. In recent years, epigenetic aberrations have been increasingly recognized as an important alternative mechanism of carcinogenesis and it is anticipated that substantial progress in the treatment of esophageal malignancy will likely only be made with a clearer understanding of esophageal tumor biology. Whereas genetic mutations, deletions, or allelic losses are fixed and irreversible, epigenetic abnormalities can potentially be corrected without interfering with the fundamental sequence of the target gene. Our current understanding of epigenetics in esophageal cancer, and the potential for targeted epigenetic therapy, will be the subject of this review.