Moving from Genomics to Therapeutics in Upper Gastrointestinal Cancers

摘要

Current treatment strategies in esophageal adenocar-cinomas that combine chemotherapy, radiation, and surgery have limited efficacy with high rates of recurrence and metastasis. The fact that the majority of patients with esophageal adenocarcinomas have an inherent drug resistance and/or high rate of recurrence calls for molecularly guided approaches in the design of clinical trials. The molecular analysis of these cancers has shown a remarkable complexity and pointed to key genomic and epigenomic alterations. There are several areas of genomic imbalances, including amplifications at 3q, 8q, 17q, and 20q and deletions commonly seen at 9p, 17p, and 18q.2 At the epigenetic level, promoter DNA methylation leads to silencing of several key tumor suppressor genes. While there are a large number of potential targets, only a few can regulate key cellular functions and intersect multiple signaling networks.