STI resistance

STIs that target Bcr-Abl: DASATINIB, IMATINIB, NILOTINIB

IMATINIB

change in target proteins
- mutation of ATP-binding site that prevents drug binding in the cancer cells, often due to further mutations of bcr-abl gene (heterogeneity of tumour) - secondary resistance
- sometimes see overexpression of bcr/abl or expression of other kinases (form of primary resistance)
- DASATINIB and NILOTINIB were developed to target cells that have become resistant to IMATINIB