Bosutinib Inhibits EGFR Activation in Head and Neck Cancer

被引：14

作者：

Segrelles, Carmen ^{[1
,2
,3
]}

Contreras, David ^{[1
]}

Navarro, Elena M. ^{[1
]}

Gutierrez-Munoz, Carmen ^{[1
]}

Garcia-Escudero, Ramon ^{[1
,2
,3
]}

Paramio, Jesus M. ^{[1
,2
,3
]}

Lorz, Corina ^{[1
,2
,3
]}

机构：

[1] CIEMAT, Mol Oncol Unit, Ed 70A,Ave Complutense 40, E-28040 Madrid, Spain

[2] Univ Hosp 12 Octubre, Res Inst 12 Octubre I 12, Mol Oncol, Ave Cordoba S-N, Madrid 28041, Spain

[3] Ctr Invest Biomed Red Canc CIBERONC, Madrid 28029, Spain

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2018年 / 19卷 / 07期

关键词：

head and neck cancer; targeted therapies; EGFR inhibitors; Bosutinib; Alpelisib; cancer cell lines; SQUAMOUS-CELL CARCINOMA; GENOMIC CHARACTERIZATION; PLUS CETUXIMAB; RESISTANCE; SRC; SYNERGISM; DRUGS;

D O I：

10.3390/ijms19071824

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and although new therapeutic approaches have been recently evaluated, overall patient survival is still poor. Thus, new effective and selective clinical treatments are urgently needed. An analysis of data from large-scale, high-throughput drug screening cell line projects identified Bosutinib, a Src/Abl inhibitor that is currently used for the treatment of chronic myelogenous leukemia, as a candidate drug to treat HNSCC. Using a panel of HNSCC-derived cell lines, we found that treatment with Bosutinib reduced cell proliferation and induced apoptosis of sensitive cell lines. The drug rapidly inhibited Src and EGFR (epidermal growth factor receptor) phosphorylation, and sensitivity to Bosutinib was correlated with the activation status of EGFR. Similar findings were observed in in vivo xenograft assays using HNSCC derived cells. Moreover, in the presence of mutations in PIK3CA, the combination of Bosutinib with the PI3K alpha inhibitor Alpelisib showed a synergistic effect. These results suggest that Bosutinib could be a new effective drug for the treatment of HNSCC, particularly in tumors with high EGFR activity. Its combination with Alpelisib could especially benefit patients bearing activating mutations of PIK3CA.

引用

页数：14