Gastroesophageal Cancer: Outcomes and Therapeutic Management

Dear Colleagues,

Gastroesophageal malignancies are a diverse group of cancers affecting the stomach, gastroesophageal junction, and esophagus, and they constitute a major cause of cancer-related fatalities globally. Current FDA-approved therapies include chemotherapy, immune checkpoint inhibitors (ipilimumab, pembrolizumab, and nivolumab), anti-VEGFR2 inhibitors (ramucirumab), and HER2-targeted drugs. However, managing advanced/metastatic disease remains challenging. In the case of distant metastatic disease, the 5-year overall survival (OS) rate is only around 5%. As the innovation of immunotherapy and HER2-targeted therapy have improved the outcomes of advanced/metastatic disease, they are currently being investigated for use in earlier localized disease.

An era of personalized therapies is emerging, with newer molecular targets being evaluated, such as claudin 18.2 (CLDN18.2), Dickkopf-1 protein (DKK1), tyrosine kinase inhibitors, and fibroblast growth factor receptor-2 (FGFR2). For instance, zolbetuximab, a monoclonal antibody targeting the tight junction protein CLDN-18.2, has shown promising results among patients with HER2-negative, CLDN-18-positive gastroesophageal cancer. While most of these biomarkers require tissue biopsy, blood-based assays are rapidly evolving, with circulation cell-free DNA (cfDNA) being used to detect genetic alterations. This newer, minimally invasive technology can aid in searching for molecular drug targets, monitoring treatment failure and the emergence of drug-resistant subclones, and capturing the genetic heterogeneity of tumor cells. In summary, these studies have paved the way for precision medicine’s utility in gastroesophageal cancer, providing hope for this challenging disease. As a result, we must continue to widen our knowledge of the precision treatment of gastroesophageal malignancies in clinical practice.

Dr. Michael K. Gibson
Guest Editor

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• gastroesophageal cancer
• targeted therapy
• circulating tumor DNA
• precision medicine
• immune checkpoint inhibitors
• esophageal cancer
• gastric cancer
• biomarkers
• molecular characterization