吉非替尼
威罗菲尼
埃罗替尼
癌症研究
表皮生长因子受体
黑色素瘤
神经母细胞瘤RAS病毒癌基因同源物
体内
酪氨酸激酶
表皮生长因子受体抑制剂
生物
医学
癌症
受体
克拉斯
内科学
结直肠癌
生物技术
转移性黑色素瘤
作者
István Kenessey,Zsófia Kramer,Lilla István,Mihály Cserepes,Tamás Garay,Balázs Hegedûs,Judit Dobos,József Tı́már,József Tóvári
出处
期刊:Melanoma Research
[Ovid Technologies (Wolters Kluwer)]
日期:2018-12-01
卷期号:28 (6): 536-546
被引量:18
标识
DOI:10.1097/cmr.0000000000000488
摘要
Oncogenic activation of the epidermal growth factor receptor (EGFR) signaling pathway occurs in a variety of tumor types, albeit in human melanoma, the contribution of EGFR is still unclear. The potential role of EGFR was analyzed in four BRAF-mutant, one NRAS-mutant and one wild-type NRAS-BRAF-carrying human melanoma cell lines. We have tested clinically available reversible tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, irreversible EGFR-TKI pelitinib and a reversible experimental compound PD153035 on in-vitro proliferation, apoptosis, migration as well as in-vivo metastatic colonization in a spleen-liver model. The presence of the intracellular domain of EGFR protein and its constitutive activity were demonstrated in all cell lines. Efficacies of EGFR-TKIs showed significant differences, and irreversible inhibition had the strongest antitumor potential. Compared with BRAF-mutant cells, wild-type BRAF was associated with relative resistance against gefitinib. In combination with gefitinib, selective mutant BRAF-inhibitor vemurafenib showed additive effect in all BRAF-mutant cell lines. Treatment of BRAF-mutant cells with gefitinib or pelitinib attenuated in-vitro cell migration and in-vivo colonization. Our preclinical data suggest that EGFR is a potential target in the therapy of BRAF-mutant malignant melanoma; however, more benefits could be expected from irreversible EGFR-TKIs and combined treatment settings.
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