@Article{096504016X14586627440192,
AUTHOR = {Arya Sobhakumari, Kevin P. Orcutt, Laurie Love-Homan, Christopher E. Kowalski, Arlene D. Parsons, C. Michael Knudson, Andrean L. Simons},
TITLE = {2-Deoxy-d-glucose Suppresses the In Vivo Antitumor Efficacy of Erlotinib  in Head and Neck Squamous Cell Carcinoma Cells},
JOURNAL = {Oncology Research},
VOLUME = {24},
YEAR = {2016},
NUMBER = {1},
PAGES = {55--64},
URL = {http://www.techscience.com/or/v24n1/56610},
ISSN = {1555-3906},
ABSTRACT = {Poor tumor response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a significant challenge for effective treatment of head and neck squamous cell carcinoma (HNSCC). Therefore, 
strategies that may increase tumor response to EGFR TKIs are warranted in order to improve HNSCC patient 
treatment and overall survival. HNSCC tumors are highly glycolytic, and increased EGFR signaling has been 
found to promote glucose metabolism through various mechanisms. We have previously shown that inhibition of glycolysis with 2-deoxy-d-glucose (2DG) significantly enhanced the antitumor effects of cisplatin and 
radiation, which are commonly used to treat HNSCC. The goal of the current studies is to determine if 2DG 
will enhance the antitumor activity of the EGFR TKI erlotinib in HNSCC. Erlotinib transiently suppressed 
glucose consumption accompanied by alterations in pyruvate kinase M2 (PKM2) expression. 2DG enhanced 
the cytotoxic effect of erlotinib in vitro but reversed the antitumor effect of erlotinib in vivo. 2DG altered the 
N-glycosylation status of EGFR and induced the endoplasmic reticulum (ER) stress markers CHOP and BiP 
in vitro. Additionally, the effects of 2DG+erlotinib on cytotoxicity and ER stress in vitro were reversed by 
mannose but not glucose or antioxidant enzymes. Lastly, the protective effect of 2DG on erlotinib-induced 
cytotoxicity in vivo was reversed by chloroquine. Altogether, 2DG suppressed the antitumor efficacy of erlotinib in a HNSCC xenograft mouse model, which may be due to increased cytoprotective autophagy mediated 
by ER stress activation.},
DOI = {10.3727/096504016X14586627440192}
}