Emerging strategies in the treatment of advanced esophageal, gastroesophageal junction, and gastric cancer: the introduction of targeted therapies

Abstract

Upper gastrointestinal malignancies are major causes of morbidity and mortality worldwide. Despite the results of recent clinical trials with new chemotherapy strategies showing encouraging activity and efficacy, the prognosis of patients with advanced gastric, gastroesophageal junction and esophageal cancer remains poor. The demonstration in other tumor types of the effectiveness of anticancer drugs with a targeted mechanism of action, interfering with pathways involved in tumor growth and spread, has opened a new era in drug development. In patients with advanced colorectal cancer, the introduction of epidermal growth factor receptor (EGFR) inhibitors and antiangiogenic agents has resulted in a significant increase in antitumor activity and survival. These targeted agents are currently being also evaluated in other tumor types including these upper gastrointestinal malignancies. These targeted agents include, among others, EGFR inhibitors, antiangiogenic agents, cell-cycle inhibitors, apoptosis promoters, and matrix metalloproteinase (MMP) inhibitors. The emerging data from the clinical development of these compounds provide novel opportunities in the treatment of these common malignancies that will probably translate into clinical benefit for patients with these diseases. This review describes the preclinical rationale and the current status of the clinical development of these compounds in patients with gastroesophageal neoplasms.