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

被引：55

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

页码：365 / 377

页数：13

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