Biomarker for her2-positive cancer and anti-her2 therapy and applications thereof

Abstract

The present invention provides MEL-18, which is a biomarker for human epidermal growth factor receptor2 (HER2)-positive cancer and anti-HER2 therapy, and a use thereof. According to the present invention, MEL-18 is a prognostic factor or predictor for a response of subjects to an anti-HER2-targeted drug in HER2-POSITIVE cancer and may be used in companion diagnostics for HER2-targeted drugs in subjects with HER2-positive cancer. Therefore, HER2-positive cancer may be more effectively treated by overcoming resistance to HER2 therapeutic agents and enhancing therapeutic efficacy by determining whether ADAM10/17 inhibitors are administered or co-administered with HER2-targeted drugs.

1 . A method of screening drugs for improving resistance to HER2-targeted drugs or being co-administrated with HER2-targeted drugs, the method comprising:
 contacting candidate materials with one or more selected from the group consisting of MEL-18 genes, MEL-18 proteins, ADAM10 genes, ADAM10 proteins, ADAM17 genes and ADAM17 proteins, and   selecting the candidate material that increases the copy number of the MEL-18 gene, the mRNA expression level of the MEL-18 gene, or the expression level of MEL-18 protein expressed from the MEL-18 gene; or inhibits the expression level(s) of the ADAM10 and/or ADAM17 gene(s) or the expression level of a protein expressed from the gene(s).   
     
     
         2 . The method of  claim 1 , wherein the gene copy number; the mRNA expression level of the MEL-18 gene; or the expression level of the MEL-18 protein is measured by a method selected from the group consisting of fluorescent in situ hybridization (FISH), comparative genomic hybridization (CGH-based array), a single nucleotide polymorphism (SNP) array, sequence assembly comparison, paired-end sequencing, multiplex ligation dependent probe amplification (MLPA), multiplex amplifiable probe hybridization (MAPH), quantitative multiplex PCR of short fluorescent fragments (QMPSF), microsatellite genotyping, Southern blotting, immunohistochemistry polymerase chain reaction (PCR), quantitative PCR (qPCR), quantitative real-time PCR (qRT-PCR), real-time PCR, microarray-based comparative genomic hybridization and ligase chain reaction (LCR). 
     
     
         3 . The method of  claim 1 , wherein the HER2-targeted drugs are selected from the group consisting of trastuzumab, pertuzumab and trastuzumab emtansine (T-DMI).