Emerging tyrosine kinase inhibitors for head and neck cancer

ABSTRACT

Introduction

Conventional regimens for head and neck squamous cell carcinoma (HNSCC) are limited in efficacy and are associated with adverse toxicities. Food and Drug Administration (FDA) approved molecular targeting agents include the HER1 (EGFR)-directed monoclonal antibody cetuximab and the immune checkpoint inhibitors nivolumab and pembrolizumab. However, clinical benefit is only seen in roughly 15–20% of HNSCC patients treated with these agents. New molecular targeting agents are needed that either act with monotherapeutic activity against HNSCC tumors or enhance the activities of current therapies, particularly immunotherapy. Small-molecule tyrosine kinase inhibitors (TKIs) represent a viable option toward this goal.

Areas covered

This review provides an update on TKIs currently under investigation in HNSCC. We focus our review on data obtained and trials underway in HNSCC, including salivary gland cancers and nasopharyngeal carcinomas, but excluding thyroid cancer and esophageal cancer.

Expert opinion

While some emerging TKIs have shown clinical benefit, the positive effects have, largely, been modest. The design of clinical trials of TKIs has been hampered by a lack of understanding of biomarkers that can be used to define patient populations most likely to respond. Further preclinical and translational studies to define biomarkers of TKI response will be critically important.

KEYWORDS:

• Head and neck squamous cell carcinoma
• tyrosine kinase inhibitor
• immunotherapy
• receptor tyrosine kinase

Declaration of interests

DE Johnson and JR Grandis are co-inventors of cyclic STAT3 decoy and have financial interests in Bluedot Bio. Bluedot Bio holds an interest in cyclic STAT3 decoy. The cyclic STAT3 decoy is not relevant to the current publication. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the following grants: NIH R35CA231998 (JR Grandis), R01DE023685 (JR Grandis and DE Johnson), and R01DE028289 (DE Johnson and JR Grandis).