Understanding how kinase-targeted therapies work

摘要: Kinases are central nodes in the cellular pathways that control differentiation, proliferation, apoptosis, motility and invasion. Most if not all human tumors thought to bear alterations one or multiple kinase genes which therefore represent attractive therapeutic targets. Accordingly, intense drug discovery programs have led development of clinically effective inhibitors. The road generate a inhibitor requires, initial phase, validation oncogenic potential corresponding gene cancer cells. As catalytic domains kinases highly homologous, most inhibitors predicted affect kinases. It is important ensure interest acts by direct inhibition its putative target. To address these issues, we devised strategy genetically inactivate activity given This approach generates isogenic cells certain expressed but devoid enzymatic thus mimicking chronic pharmacological treatment with specific selective inhibitor. limited could be broadly applicable any drug/protein combination target domain known.