Human Blood Serum Counteracts EGFR/HER2-Targeted Drug Lapatinib Impact on Squamous Carcinoma SK-BR-3 Cell Growth and Gene Expression

Biochemistry (Moscow)(2024)

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摘要
Lapatinib is a targeted therapeutic inhibiting HER2 and EGFR proteins. It is used for the therapy of HER2-positive breast cancer, although not all the patients respond to it. Using human blood serum samples from 14 female donors (separately taken or combined), we found that human blood serum dramatically abolishes the lapatinib-mediated inhibition of growth of the human breast squamous carcinoma SK-BR-3 cell line. This antagonism between lapatinib and human serum was associated with cancelation of the drug induced G1/S cell cycle transition arrest. RNA sequencing revealed 308 differentially expressed genes in the presence of lapatinib. Remarkably, when combined with lapatinib, human blood serum showed the capacity of restoring both the rate of cell growth, and the expression of 96.1
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关键词
EGFR,Erbb2,HER-targeted cancer therapy,human blood serum,lapatinib,EGF,squamous cell carcinoma,SK-BR-3 cells,drug resistance,transcriptome profiling
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