Update on Gastroesophageal Adenocarcinoma Targeted Therapies

Hematol Oncol Clin North Am. 2017 Jun;31(3):511-527. doi: 10.1016/j.hoc.2017.01.009.

Abstract

Gastroesophageal cancer (GEC) remains a major cause of cancer-related mortality worldwide. Although the incidence of distal gastric adenocarcinoma (GC) is declining in the United States, proximal esophagogastric junction adenocarcinoma (EGJ) incidence is rising. GC and EGJ, together, are treated uniformly in the metastatic setting as GEC. Overall survival in the metastatic setting remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to date-only first-line anti-HER2 therapy for ERBB2 amplification and second-line anti-VEGFR2 therapy. This article reviews aberrations in epidermal growth factor receptor, MET, and ERBB2, their therapeutic implications, and future directions in targeting these pathways.

Keywords: ERBB2; Epidermal growth factor receptor; Gastric; Gastroesophageal; HER2; MET; Targeted; Treatment.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / enzymology
  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / enzymology
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / pathology
  • Esophagogastric Junction* / enzymology
  • Esophagogastric Junction* / pathology
  • Gene Amplification
  • Humans
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / enzymology
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology
  • Survival Rate
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Antineoplastic Agents
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • KDR protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2
  • Vascular Endothelial Growth Factor Receptor-2