Dasatinib

Tyrosine kinase inhibitor for the treatment of oncological diseases ( orphan drug).

The translocation between chromosomes 9 and 22 is characteristic of chronic myeloid leukemia (CML) (Philadelphia chromosome). This leads to the oncogene known as BCR-ABL.

This oncogene is a cytoplasmic tyrosine kinase that phosphorylates various substrates. BCR-ABL inhibits normal cell proliferation and differentiation.

Imatinib inhibits the BCR-ABL tyrosine kinase activity. It specifically blocks the binding site for ATP at the tyrosine kinase BCR-ABL. This inhibits the transfer of ATP phosphate groups to tyrosine residues of the substrates.

In this way, signal transduction within cells is prevented. Thus, processes of migration, invasion angiogenesis, proliferation and anti-apoptosis are disturbed.

1. Gabrielli A et al (2007) Stimulatory autoantibodies to the PDGF receptor: a link to fibrosis in scleroderma and a pathway for novel therapeutic targets. Autoimmune Rev 7: 121-126
2. Gabrielli A et al (2007) Pathogenic autoantibodies in systemic sclerosis. Curr Opin Immunol 19: 640-645
3. Goldman JM et al (2003) Chronic myeloid leukemia - advances in biology and new approaches to treatment. N Engl J Med 349: 1451-1464
4. Kähler HC et al. (2009) Skin changes caused by "targeted therapies" in oncological patients. Dermatologist 60: 433-440
5. Svegliati S et al (2007) Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood 110: 237-241