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Resistance to Anti-HER2 Therapies in Gastrointestinal Malignancies

Christiana Mo1,2, Michelle Sterpi1,2, Hyein Jeon1,2

  • 1Department of Medical Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Cancers
|August 29, 2024
PubMed

Insights

Human epidermal growth factor 2 (HER2) drives cancer growth. This review explores HER2-positive gastrointestinal cancers, therapies, and resistance mechanisms limiting treatment effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Human epidermal growth factor 2 (HER2) is a key receptor tyrosine kinase implicated in cellular growth and proliferation.
  • HER2 overexpression/amplification is a driver in various malignancies, including gastrointestinal cancers.
  • Targeting HER2 has been a focus of cancer research for decades.

Purpose of the Study:

  • To review current HER2 expression patterns and therapeutic strategies for gastrointestinal malignancies.
  • To analyze mechanisms of drug resistance in HER2-positive cancers.
  • To identify challenges and future directions in HER2-targeted therapy.

Main Methods:

  • Comprehensive literature review of HER2 expression, therapies, and resistance mechanisms.
  • Analysis of data from landmark clinical trials, including the ToGA trial.
  • Synthesis of information on gastroesophageal, colorectal, biliary tract, and small bowel cancers.

Main Results:

  • HER2-positive gastrointestinal malignancies present diverse expression patterns.
  • Established therapies show efficacy but are often limited by acquired drug resistance.
  • Specific resistance mechanisms, including pathway reactivation and target mutation, hinder treatment effectiveness.

Conclusions:

  • Despite advances, drug resistance remains a significant hurdle in treating HER2-positive gastrointestinal cancers.
  • Understanding resistance mechanisms is crucial for developing more effective therapeutic strategies.
  • Further research is needed to overcome resistance and improve outcomes for patients with HER2-driven malignancies.
Keywords:
HER2cancer therapeuticscolorectal cancergastro/gastroesophageal cancerresistance

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