ErbB2/HER2: Its Contribution to Basic Cancer Biology and the Development of Molecular Targeted Therapy

摘要: ErbB2, one of the receptor tyrosine kinase superfamily has attracted attention cancer researchers since its discovery. Thirty years ago, ErbB2 was discovered as an oncogene that transforms NIH3T3 cells. The first decade research revealed it is a member ErbB family and deregulated in various types human cancer. In second decade, significant discovery came from crystallography with rational theory explains why no ligands specific for have been identified so far, other breakthrough clinical field appearance ErbB-targeted therapeutics. Today, strive to describe elaborate signaling network receptors by proteomic analysis, our knowledge their function, which far complete, being applied develop more efficient therapeutics patients. We will begin story called neu. dawn research, this gene, derived rat tumor, classified most pivotal genes cancer, along oncogenes Ras Myc tumor suppressor gene p53. This because frequently amplified overexpressed certain cancers, such breast carcinoma. Similar oncogenes, subsequent demonstrated indispensable role development. Now, interest whether acts on same target proteins normal networks downstream are complex there each receptor, except composition dimer seems define targets. For example, EGFR (epidermal growth factor receptor)-containing heterodimers prefer stimulate mitogen-activated protein (MAPK) cascade, while ErbB3-containing dimers preferably activate phosphatidylinositol 3kinase (PI3K). characteristic reflected difficulty choosing best corresponding case clinic.