Is dasatinib a targeted drug and which gene it targets?

Dasatinib (Dasatinib) is a targeted drug. The gene it primarily targets is BCR-ABL, a gene that is abnormally active in some leukemia patients. Dasatinib blocks the growth and spread of cancer cells by inhibiting the activity of the BCR-ABL gene. In addition, dasatinib also shows certain targeting effects on some other related genes.

Dasatinib is a tyrosine kinase inhibitor with multiple targets. At nanomolar concentrations, it inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2 and PDGFRβ. In patients with chronic myelogenous leukemia (CML), the tyrosine kinase activity of BCR-ABL is dysregulated, leading to the growth, proliferation, and survival of cancerous hematopoietic cells. Dasatinib binds to both active and inactive conformations of the ABL kinase domain with higher affinity than imatinib. Dasatinib inhibits cell growth in chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines that overexpress BCR-ABL.

In addition, dasatinib has in vitro activity against leukemia cell lines that are sensitive or resistant to imatinib. It has been suggested that dasatinib can overcome imatinib resistance caused by mutations in the BCR-ABL kinase domain because it does not need to interact with some of the residues involved in these mutations. Under experimental conditions, dasatinib can overcome imatinib resistance caused by BCR-ABL kinase domain mutations, activation of alternative signaling pathways involving SRC family kinases (LYN, HCK), and overexpression of multidrug resistance genes.