Profiling and Cross-Talk of Tyrosine Phosphorylation with Lysine Acetylation and Succinylation in Tyrosine Kinase Inhibitor Resistant Breast Cancer Cells

摘要

Human epidermal growth factor receptor 2 (HER2) is a member of the type I transmembrane receptor kinase family and regulates cell growth and differentiation. Overexpression of HER2 is found in over 25% of breast cancer cells, and is indicative of a poor clinical outcome. Selective HER2 inhibitors were developed to treat cancers that become resistant to the monoclonal antibody trastuzumab, which is used as a standard therapy in these cancers. Of these, lapatinib is the one with best specificity and this inhibits both HER2 and EGFR tyrosine kinases. Unfortunately, resistance to lapatinib has also been observed within 12 months of starting therapy. In this case, the inhibition of HER2 kinase is thought to activate redundant survival pathways, which leads to resistance.