Harnessing biomarkers of response to improve therapy selection in esophago-gastric adenocarcinoma

Pharmacogenomics. 2021 Jul;22(11):703-726. doi: 10.2217/pgs-2020-0090. Epub 2021 Jun 14.

Abstract

Advanced esophago-gastric (OG) adenocarcinomas have a high mortality rate and new therapeutic options are urgently required. Despite recent advances in understanding the molecular characteristics of OG cancers, tumor heterogeneity poses a challenge in developing new therapeutics capable of improving patient outcomes. Consequently, chemotherapy remains the mainstay of systemic treatment, with the HER2 being the only predictive biomarker routinely targeted in clinical practice. Recent data indicate that immunotherapy will be incorporated into first-line chemotherapy, but further research is required to refine patient selection. This review will summarize the clinical strategies being evaluated to utilize our knowledge of predictive biomarkers with reference to novel therapeutics, and discuss the barriers to implementing precision oncology in OG adenocarcinoma.

Keywords: biomarkers of response; esophageal cancer; esophago-gastric adenocarcinoma; gastric cancer; gastro-esophageal junction cancer; precision oncology; predictive biomarkers; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / therapy*
  • Biomarkers / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / therapy*
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immunoconjugates / administration & dosage
  • Immunotherapy / methods
  • Immunotherapy / trends
  • Precision Medicine / methods*
  • Precision Medicine / trends
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Stomach Neoplasms / drug therapy
  • Trastuzumab / administration & dosage

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Immunoconjugates
  • trastuzumab deruxtecan
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Camptothecin