Perspectives of HER2-targeting in gastric and esophageal cancer

ABSTRACT

Introduction: The blockade of HER2 signaling has significantly improved the outlook for esophagogastric cancer patients. However, targeting HER2 still remains challenging due to complex biology of this receptor in gastric and esophageal cancers.

Areas covered: Here, we review complex HER2 biology, current methods of HER2 testing and tumor heterogeneity of gastroesophageal cancer. Ongoing and completed clinical research data are discussed.

Expert opinion: HER2 overexpression is a validated target in gastroesophageal cancer, with therapeutic implications resulting in prolonged survival when inhibited in the front-line setting. With standardized HER2 testing in gastro-esophageal cancer, the ongoing trials are testing newer agents and combinations including combination of anti-HER2 antibodies with immunotherapy. Clonal heterogeneity and emergence of resistance will challenge our approach to treating these patients beyond the frontline settings.

KEYWORDS:

• HER2
• ErbB2
• trastuzumab
• gastric cancer
• esophageal cancer

Article Highlights

• HER2, a tyrosine kinase receptor overexpressed or mutated in a variety of cancers, has been identified as an important therapeutic target and esophageal and gastric cancers.

• All advanced-stage gastroesophageal cancers should be tested for HER2 amplification or mutation at the time metastatic disease is diagnosed.

• Pharmacologic targeting of HER2 with trastuzumab, in combination with platinum and fluoropyrimidine-based systemic cytotoxic therapy, has improved survival in patients with advanced disease

• Targeting HER2 beyond disease progression and with novel agents or combinations of agents remain areas of active investigation.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by NIH core grant CA-06927, by the Pew Charitable Fund, and by a generous gift from Mrs. Concetta Greenberg to Fox Chase Cancer Center. I. Astsaturov was also supported by NIH grants R01 CA188430, K22 CA160725, R21 CA164205, a career development award from Genentech; by Tobacco Settlement funding from the State of Pennsylvania, and by a grant from the Bucks County Board of Associates.