Overcoming cetuximab resistance in HNSCC: The role of AURKB and DUSP proteins

被引：54
作者：
Boeckx, Carolien [1 ]
de Beeck, Ken Op [1 ,2 ,3 ]
Wouters, An [1 ]
Deschoolmeester, Vanessa [1 ]
Limame, Ridha [1 ]
Zwaenepoel, Karen [4 ]
Specenier, Pol [1 ,5 ]
Pauwels, Patrick [1 ,4 ]
Vermorken, Jan B. [1 ,5 ]
Peeters, Marc [1 ,5 ]
Van Camp, Guy [2 ,3 ]
Baay, Marc [1 ]
Lardon, Filip [1 ]
机构：
[1] Univ Antwerp, CORE Antwerp, Lab Canc Res & Clin Oncol, Antwerp, Belgium
[2] Univ Antwerp, Ctr Med Genet, Dept Biomed Sci, Antwerp, Belgium
[3] Univ Antwerp Hosp, Antwerp, Belgium
[4] Univ Antwerp Hosp, Dept Pathol, Antwerp, Belgium
[5] Univ Antwerp Hosp, Dept Med Oncol, Antwerp, Belgium
来源：
CANCER LETTERS | 2014年 / 354卷 / 02期
关键词：
Head and neck squamous cell carcinoma; Anti-EGFR therapy; Cetuximab resistance; Dual-specificity phosphatase 5 and 6; Aurora kinase B; Nano Pro 1000; SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITORS; APIGENIN INDUCES APOPTOSIS; NECK-CANCER; COLORECTAL-CANCER; PANCREATIC-CANCER; MESENCHYMAL TRANSITION; AURORA KINASES; MONOCLONAL-ANTIBODY;
D O I：
10.1016/j.canlet.2014.08.039
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Unraveling the underlying mechanisms of cetuximab resistance in head and neck squamous cell carcinoma (HNSCC) is of major importance as many tumors remain non-responsive or become resistant. Our microarray results suggest that "resistant" cells still exhibit RAS-MAPK pathway signaling contributing to drug resistance, as witnessed by low expression of DUSP5 and DUSP6, negative regulators of ERK1/2, and increased expression of AURKB, a key regulator of mitosis. Therefore, interrupting the RAS-MAPK pathway by an ERK1/2 inhibitor (apigenin) or an AURKB inhibitor (barasertib) might be a new strategy for overcoming cetuximab resistance in HNSCc. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：365 / 377
页数：13
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