Targeted therapies for gastroesophageal cancers

Abstract

Gastroesophageal cancers are some of the most common malignancies worldwide. A significant portion of patients are diagnosed with advanced or metastatic disease given the insidious nature of gastroesophageal cancers. In the instance where surgical resection for cure is no longer an option, the prognosis is poor and generally less than a year. Traditionally, standard front-line chemotherapy included two- to three-drug regimens with modest improvements in overall survival. Over the past two decades, with increased understanding of the biology of cancer, targeted therapies have been developed to stop the actions of molecules that are key in the growth and spread of cancer cells and have been successful in a number of cancers. In gastroesophageal cancer, these gains have been more modest with limited approval-trastuzumab being incorporated into front-line use in HER2-positive disease, and ramucirumab alone or in combination with paclitaxel becoming the preferred second-line regimen in progressive disease. However, with increased understanding of the biology of cancer, new and promising targeted therapies have emerged along with novel strategies in combining targeted therapies with traditional chemotherapy and immunotherapy. In this article, we will review the use of targeted therapies in the treatment of gastroesophageal cancer and touch upon future treatment strategies and therapeutics currently under investigation.

Keywords: Gastric cancer; esophageal cancer; gastroesophageal cancer; ramicurumab; targeted therapy; trastuzumab.

Figure 1

Monoclonal antibodies and tyrosine receptor kinase inhibitors and their targets in gastroesophageal cancer—mesenchymal-epithelial transition (MET), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), claudin-18 isoform 2 (Claudin 18.2), rapidly accelerated fibrosarcoma (Raf), mammalian target of rapamycin (mTOR).