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Updated: Jan 6, 2026

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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Emerging EGFR-Targeted Therapy in Head and Neck Cancer: A Review

Woochan Hwang1,2, Jong Seok Ahn1,2, Hyun Ae Jung1,3

  • 1Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital, Boston.

JAMA Oncology
|September 25, 2025
PubMed
Abstract

Insights

New therapies targeting the epidermal growth factor receptor (EGFR) show promise for advanced head and neck squamous cell carcinoma (HNSCC). However, efficacy is limited in human papillomavirus (HPV)-positive HNSCC, requiring further research.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is a major health concern with limited treatment options for advanced stages.
  • Epidermal growth factor receptor (EGFR) is frequently overexpressed in HNSCC, making it a key therapeutic target.
  • Current EGFR-targeted therapies offer modest clinical benefits in HNSCC.

Purpose of the Study:

  • To review the evolving landscape of EGFR-targeted therapeutics for HNSCC.
  • To present the biological rationale and early-phase trial results of novel EGFR-targeting agents.
  • To discuss future directions for improving treatment efficacy in HNSCC.

Main Methods:

  • Review of current literature on EGFR-targeted therapies in HNSCC.
  • Analysis of novel therapeutic agents including bispecific antibodies, antibody-drug conjugates, immune cell engagers, and adaptive cell therapies.
  • Examination of clinical trial data for emerging EGFR-targeting approaches.

Main Results:

  • Cetuximab-based combination regimens and novel agents are being investigated.
  • Early-phase trials show potential for new therapeutic strategies.
  • EGFR-targeted therapies demonstrate reduced efficacy in human papillomavirus (HPV)-positive HNSCC.

Conclusions:

  • Emerging combinatorial approaches and novel EGFR-targeting agents offer new hope for advanced HNSCC.
  • Future progress requires a deeper understanding of tumor biology and innovative strategies to mitigate toxicity.
  • Improving efficacy in the growing population of HPV-positive HNSCC patients is crucial.

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