Targeting pathways mediating resistance to anti-EGFR therapy in squamous cell carcinoma of the head and neck

ABSTRACT

Introduction: As epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of squamous cell carcinomas of the head and neck (SCCHN), several therapeutic agents that target EGFR have been evaluated for the treatment of SCCHN. Although patients with SCCHN derive clinical benefit from anti-EGFR agents, most notably the EGFR monoclonal antibody cetuximab, these patients eventually become resistant to EGFR-based therapies; preclinical studies have shown activation of secondary signaling pathways that lead to resistance to EGFR inhibition and, as such, serve as potential therapeutic targets to overcome resistance to EGFR inhibitors.

Areas covered: This review summarizes the results of recently completed trials of anti-EGFR agents in SCCHN, highlights the various mechanisms that drive resistance to EGFR inhibitors in SCCHN, and focuses on several novel targeted agents that could potentially help overcome resistance to EGFR-based therapies in SCCHN.

Expert commentary: Due to the development of resistance to EGFR-targeted therapies, novel treatment approaches to overcome resistance are a key unmet need for SCCHN.

KEYWORDS:

• Squamous cell carcinoma of the head and neck
• resistance
• EGFR
• targeted therapy
• clinical trials

Acknowledgments

Writing, editorial support, and formatting assistance was provided by Jason Jung, PhD, of MedErgy, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Declaration of interest

T Hensing has received advisory board fees and honoraria from Novartis, Astra Zeneca and Genentech. B Brockstein has received advisory board fees and honoraria from Novartis, Bristol Myers-Squibb, Bayer and Astra Zeneca. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This work was supported by the Boehringer Ingelheim Pharmaceuticals, Inc.