The role of tumor suppressor genes in esophageal cancer

Esophageal cancer remains one of the 10 most common cancers worldwide. Although patients with early lesions have a reasonable prognosis, most patients present with advanced disease resulting in an overall 5-year survival of 5-10%. Therefore, the current challenges in the management of esophageal cancer are to obtain a better understanding of the underlying molecular biological alterations to provide new treatment options. During the development of esophageal cancer, there is progression from a premalignant epithelium to a neoplasm that frequently demonstrates a heterogeneous mix of genetic alterations. The vast majority of esophageal cancers have inactivation of the p53 and p16 genes at an early stage followed by defects in genes such as APC, Rb and cyclin D1 at later stages of progression. There is also mounting evidence that numerous, specific regions throughout the genome are frequently lost in these cancers. As a result, we will in the next decade, likely see the discovery and characterizations of novel tumor suppressor genes that may be important in the development of esophageal cancer. The accumulating knowledge about the inactivation of the tumor suppressor genes could ultimately provide us with objective diagnostic tools, more accurate markers for prediction of malignant transformation from premalignant epithelium and facilitate the introduction of novel therapeutic options for the management of esophageal cancer.