TY - JOUR
T1 - Novel targets in HPV-negative head and neck cancer
T2 - Overcoming resistance to EGFR inhibition
AU - Burtness, Barbara
AU - Bauman, Julie E.
AU - Galloway, Thomas
N1 - Funding Information:
We searched PubMed for articles published in English between January, 2007, and November 30, 2012. The terms searched were “c-Met”, “aurora kinase”, “nuclear EGFR”, “HDAC”, “mTOR inhibition”, “Jak/STAT”, AND “head and neck cancer”. All original research articles were assessed for relevance and, after excluding articles related to thyroid cancer, salivary gland cancer, or oesophageal cancer, references lists were scanned for further studies. The final reference list was generated on the basis of originality and relevance to the scope of this Review. Contributors BB was responsible for the conception of the Review and for correspondence. BB and JEB provided the figures. All authors contributed to the literature search, writing of the manuscript, and approved the final version. Conflicts of interest BB receives research funding from Curis Pharmaceuticals, Boehringer Ingelheim, and Genentech, and has consulted for Bristol-Myers Squibb. JEB is a scientific consultant to Aveo Pharmaceuticals.
PY - 2013/7
Y1 - 2013/7
N2 - Cancers of the head and neck that arise from habitual exposure to carcinogens have lower cure rates than those that arise from infection with human papillomavirus (HPV), and intensification of cytotoxic chemotherapy and radiation has not improved outcomes. HPV-negative head and neck cancers abundantly express EGFR, and the monoclonal antibody cetuximab, directed against EGFR, is the only targeted therapy that has improved disease survival so far. However, response rates to single-agent cetuximab are lower than 15%, and cetuximab given with chemotherapy or radiation leads to only a modest effect on survival. Thus, investigating the mechanisms of resistance to EGFR inhibition in HPV-negative head and neck cancer might help identify novel and active therapies. In this Review, we focus on therapies in development that target redundant receptor tyrosine kinases (eg, HER2 and MET), reduce or abrogate nuclear functions of EGFR, affect cellular trafficking by inhibition of histone deacetylase, or treatments that might address resistance that arises in the EGFR signalling stream (eg, aurora-kinase inhibitors and STAT decoys).
AB - Cancers of the head and neck that arise from habitual exposure to carcinogens have lower cure rates than those that arise from infection with human papillomavirus (HPV), and intensification of cytotoxic chemotherapy and radiation has not improved outcomes. HPV-negative head and neck cancers abundantly express EGFR, and the monoclonal antibody cetuximab, directed against EGFR, is the only targeted therapy that has improved disease survival so far. However, response rates to single-agent cetuximab are lower than 15%, and cetuximab given with chemotherapy or radiation leads to only a modest effect on survival. Thus, investigating the mechanisms of resistance to EGFR inhibition in HPV-negative head and neck cancer might help identify novel and active therapies. In this Review, we focus on therapies in development that target redundant receptor tyrosine kinases (eg, HER2 and MET), reduce or abrogate nuclear functions of EGFR, affect cellular trafficking by inhibition of histone deacetylase, or treatments that might address resistance that arises in the EGFR signalling stream (eg, aurora-kinase inhibitors and STAT decoys).
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U2 - 10.1016/S1470-2045(13)70085-8
DO - 10.1016/S1470-2045(13)70085-8
M3 - Review article
C2 - 23816296
AN - SCOPUS:84879707249
VL - 14
SP - e302-e309
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 8
ER -