HGFR and FGR2: Their Roles in Progression and Metastasis of Esophageal Cancer

Abstract

Esophageal cancer (EC) is the sixth leading cause of malignancy-related death in the world. The disease is characterized by two types of histologies: esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC), which are the most common in the Western world. While alcohol has proven to lead to ESCC, it has not been associated with EAC. Progressive dysphagia (first with solids, followed by liquids) and rapid involuntary weight loss are the two most common symptoms, which make most patients seek medical attention. Most patients have a long period of symptoms before they seek care. At diagnosis, ~50% of the patients already have metastasis. The treatment of gastroesophageal cancers continues to pose significant clinical challenges for various defined reasons. The majority of patients fail intensive and toxic multimodality therapy for locoregional disease, and systemic chemotherapy for metastatic carcinoma gives short-term benefits only. Our understanding of the molecular pathology of gastroesophageal cancers has considerably increased during the recent years, leading to the development of novel targeted therapeutic agents that have proven to be promising in improving the patients’ survival with minimal adverse events. Receptor tyrosine kinases (RTKs) play pivotal role(s) in the formation, maintenance, growth, and differentiation of the malignant cells encompassing both histological types of EC. Malignancies treated with chemotherapy/radiation therapy face the challenge of developing resistance and increasing the aggressive nature of cancerous cells leading to undesirable recurrence. In peer-reviewed literature, an array of RTKs have been described in ESCC, and more recently, they are being assessed for their therapeutic utility. Notably, structures of hepatocyte growth factor receptor (HGFR) and fibroblast growth factors receptor 2 (FGR2) are two of the many prominent RTKs studies thus far. In this chapter, we thoroughly discuss the clinical characteristics of the disease and structure-functional aspects of various RTKs with focus on HGFR and FGR2 as it relates to the translational and clinical outcomes of EC.