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Review
. 2010 Sep;15(3):355-73.
doi: 10.1517/14728214.2010.497754.

Emerging drugs to treat squamous cell carcinomas of the head and neck

Christopher Fung  1 , Jennifer R Grandis
Affiliations
Review

Emerging drugs to treat squamous cell carcinomas of the head and neck

Christopher Fung et al. Expert Opin Emerg Drugs. 2010 Sep.

Abstract

Importance of the field: Head and neck squamous cell carcinoma (HNSCC) is the eighth leading cause of cancer death worldwide. Despite advances in surgery and chemoradiation therapy, there has been little improvement in survival rates over the past 4 decades. Additionally, surgery and chemoradiotherapy have serious side effects. The development of agents with greater efficacy and tolerability is needed.

Areas covered in this review: EGFR is the only proven molecular target for HNSCC therapy. Cetuximab, the sole FDA-approved molecular targeted HNSCC therapy, and other potential targeted therapies are being evaluated in preclinical, clinical and post-marketing studies. Here, we review the emerging targets for biological agents in HNSCC and the rationale for their selection.

What the reader will gain: Key information in the development of new drug targets and the emergence of new biomarkers are discussed. Readers will gain insight regarding the limitations of current therapies, the impact of recently approved targeted therapies and the influence that predictive biomarkers will have on drug development.

Take home message: The head and neck cancer drug market is rapidly evolving. Coordination between drug and biomarker development efforts may soon yield targeted therapies that can achieve the promise of personalized cancer medicine.

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Conflict of interest statement

Declaration of interest The authors state no conflict of interest and have received no payment in preparation of this manuscript.

Figures

Figure 1
Figure 1. Targeted molecular pathways in head and neck cancer
Selected agents that are currently in clinical trials are represented here. Briefly, EGFR and VEGFR signals utilize a variety of downstream molecular pathways including the PI3K-Akt-mTOR, STAT and Ras-MAPK (ERK) pathways. Agents targeting these pathways include mAbs (cetuximab, panitumumab, necitumumab, ch806, bevacizumab), tyrosine kinase inhibitors (erlotinib, gefitinib, vandetanib, lapatinib), multikinase inhibitors (sorafenib, sunitinib), Src family kinase inhibitors (dasatinib, saracatinib), mTOR inhibitors (everolimus, temsirolimus) and nucleic acid decoy (STAT3 decoy). p53 and Rb are tumor suppressors that are inhibited by HPV proteins E6 and E7, respectively. E6 and E7 are constitutively expressed in HPV-16 and -18 infected tumor cells and are targeted by HPV peptide vaccines. Vaccination against E6 and E7 allows cytotoxic T-cell recognition of infected cells. mTOR: Mammalian target of rapamycin; STAT3: Signal transducer and activator of transcription-3.
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