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

A companion diagnostic method for HER2-targeted drugs in subjects with Human epidermal growth factor receptor 2 (HER2)-positive cancers comprising,

• measuring the copy number of MEL-18 gene;
• the mRNA expression level of the MEL-18 gene;
• and/or the expression level of MEL-18 protein in a sample obtained from the subjects with HER2-positive cancers.

A method of treating human epidermal growth factor receptor2 (HER2)-positive cancers comprising

• administering a pharmaceutical composition comprising one or more selected from the group consisting of MEL-18 gene, MEL-18 gene expression activators, MEL-18 proteins, MEL-18 protein activators, ADAM10 gene inhibitors, ADAM10 protein activity inhibitors, ADAM17 gene inhibitors, and ADAM17 protein activity inhibitors to subjects with HER2-positive cancer,
• wherein subjects have the copy number of MEL-18 gene, the mRNA expression level of the MEL-18 gene, and/or the expression level of MEL-18 protein, which are/is lower than predetermined value(s);
• and/or subjects have or expected to have drug resistance to HER2-targeted drugs.

A method for inhibiting or improving resistance of subjects with HER2-positive cancers with respect to HER2-targeted drugs comprising

• a therapeutically effective amount of one or more selected from the group consisting of MEL-18 gene, MEL-18 gene expression activators, MEL-18 proteins, MEL-18 protein activators, ADAM10 gene inhibitors, ADAM10 protein activity inhibitors, ADAM17 gene inhibitors, and ADAM17 protein activity inhibitors.

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 genes, the mRNA expression level of the MEL-18 genes, or the expression level of proteins expressed from the 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).