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HER2-positive gastric cancer: from targeted therapy to CAR-T cell therapy

Qiangzu Shao1,2, Junge Deng1,2, Haoran Wu1,2

  • 1The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.

Frontiers in Immunology
|April 4, 2025
PubMed

Insights

HER2-positive gastric cancer (GC) shows limited response to chemotherapy. Novel therapies like antibody-drug conjugates and CAR-T cells offer new options, but drug resistance remains a challenge for HER2-targeted treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Gastric cancer (GC) is a global health concern, with HER2-positive GC presenting unique challenges.
  • Conventional chemotherapy has limited efficacy for HER2-positive GC.
  • Advancements in molecular targeted therapies offer new hope for this subtype.

Purpose of the Study:

  • To summarize current HER2-targeted therapy strategies for gastric cancer.
  • To review the mechanisms of drug resistance in HER2-targeted therapy for GC.
  • To discuss potential future directions in overcoming resistance.

Main Methods:

  • Comprehensive literature review of HER2-targeted therapies for gastric cancer.
  • Analysis of resistance mechanisms associated with antibody-drug conjugates (ADCs) and chimeric antigen receptor T-cell (CAR-T) therapy.
  • Discussion of emerging therapeutic strategies and their clinical implications.

Main Results:

  • HER2-targeted therapies, including ADCs and CAR-T, have emerged as promising treatments for HER2-positive GC.
  • Tumor heterogeneity and the tumor microenvironment are key factors contributing to drug resistance.
  • Various resistance mechanisms limit the long-term effectiveness of current HER2-targeted approaches.

Conclusions:

  • Despite advancements, overcoming drug resistance is crucial for improving outcomes in HER2-positive GC.
  • Understanding resistance mechanisms is essential for developing more effective therapeutic strategies.
  • Future research should focus on combination therapies and novel approaches to enhance HER2-targeted treatment efficacy.
Keywords:
HER2cell therapydrug resistancegastric cancertargeted therapy

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