Targeted Therapy with Imatinib: An Exception or a Rule?

摘要: The discovery of STI571, a drug targeting the tyrosine kinase activity Bcr-Abl, c-Kit, and platelet-derived growth factor receptor (PDGFR), has demonstrated feasibility ATP-competitive small-molecule inhibitors for chronic treatment molecularly defined cancers. presence an activated form protein kinases targeted by STI571 in various malignancies appears to be mandatory clinical response this drug. This also indicates that certain subset tumors depends upon overactivation one or more signaling pathways, which can attacked therapy. finding resistance is often associated with mutations domain unambiguously demonstrates targets these are and/or PDGFR. Generation most likely due binding mode stabilizes inactive conformation target kinases. Recent mutational analysis combined structural biology provided basis understanding mechanisms as well activation Although key exquisite selectivity tolerability it its “weakness”, because allows occur appear not affect normal function kinase. Therefore, effective long-term cancer therapy inhibitors, necessary use than inhibitor different conformations same kinase, each needs aimed at specific mutant downstream element.