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Progress and challenges in HER2-positive gastroesophageal adenocarcinoma

Dan Zhao1, Samuel J Klempner2,3, Joseph Chao4

  • 1Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Bldg. 51, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.

Journal of Hematology & Oncology
|May 19, 2019
PubMed

Insights

HER2 heterogeneity in gastroesophageal adenocarcinoma impacts treatment. Understanding HER2 overexpression and resistance is key to developing new therapies targeting this cancer.

Area of Science:

  • Oncology
  • Gastroenterology
  • Molecular Biology

Background:

  • HER2 expression is crucial for guiding trastuzumab therapy in metastatic gastroesophageal adenocarcinoma (GEA).
  • Unlike breast cancer, other HER2-targeted therapies have not improved outcomes in GEA.
  • Spatial and intratumoral heterogeneity of HER2 overexpression is a significant challenge in GEA.

Purpose of the Study:

  • To review clinical trials of HER2-targeted agents in GEA.
  • To explore genomic and temporal heterogeneity in therapeutic resistance.
  • To discuss novel strategies for refining GEA treatment.

Main Methods:

  • Literature review of seminal clinical trials.
  • Analysis of emerging data on molecular resistance mechanisms.
  • Synthesis of current knowledge on HER2 heterogeneity in GEA.

Main Results:

  • Trastuzumab remains the primary HER2-targeted therapy for GEA.
  • HER2 heterogeneity contributes to variable treatment responses.
  • Genomic and temporal alterations drive resistance to HER2-targeted agents.

Conclusions:

  • Addressing HER2 heterogeneity is critical for improving GEA outcomes.
  • Novel HER2-targeted agents and strategies show promise for future treatment.
  • Further research into resistance mechanisms is needed to optimize therapy.
Keywords:
Circulating tumor DNAGastroesophageal cancerGenomic profilingHER2Next-generation sequencingTrastuzumabTumor heterogeneity

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