ERBB2

The protein encoded by ERBB2 belongs to the epidermal growth factor receptor family, which includes HER1 (erbB1, EGFR), HER2 (erbB2, NEU), HER3 (erbB3) and HER4 (erbB4), and also belongs to the receptor tyrosine kinase family. ERBB2 has no ligand-binding domain, but can form a heterodimer with family members to bind ligands such as epidermal growth factor (EGF), thereby activating downstream proteins such as MAPK and PI3K by phosphorylation. Overexpression of ERBB2 is found in a variety of tumors, commonly breast and ovarian cancers (PMID: 17471238, PMID: 15583858, PMID: 9130710).

FDA approved afatinib for the treatment of metastatic non-small cell lung cancer with deletion of exon 19 or L858R mutation of exon 21 of tumor epidermal growth factor receptor (EGFR). FDA also approved the following drugs for ERBB2 targeted therapy in other cancers: Neratinib has an obvious therapeutic effect on breast cancer. Herceptin can be used for HER2 overexpressing breast cancer and metastatic gastric cancer or adenocarcinoma of the gastroesophageal junction. Pertuzumab can be used for HER2 positive metastatic breast cancer. Lapatinib can be used for HER2 positive metastatic breast cancer. Ado-trastuzumab emtansine can be used in HER2 positive metastatic and recurrent breast cancer (PMID: 31548601, PMID: 24080156, PMID: 23827380, PMID: 32917240).