Question

The revolutionary leukemia drug, imatinib, is an example of targeted chemotherapy. Explain how it works to treat leukemia. How does this differ from conventional cytotoxic chemotherapy?

Answer 1

conventional chemotherapy to treat leukemia is cytotoxic because these conventional chemotherapy agents will target any enzyme, protein or any signal pathway which is present in both the normal cells as well as leukemia cells. these chemotherapy agents are unable to differentiate between normal and leukemia cells thus they are cytotoxic.

the new leukemia drug imatinib is slightly different from the conventional therapy. Imatinib is a synthetic tyrosine kinase inhibitor designed to inhibit certain protein tyrosine kinases involved in oncogenesis. it is designed to inhibit the breakpoint cluster region (BCR)-Abelson (ABL) fusion protein arises from the chromosomal abnormality known as the Philadelphia chromosome.

Imatinib binds to the ATP binding site of the BCR/ABL tyrosine kinase and stabilizes the inactive BCR/ABL. hence preventing tyrosine residue phosphorylation of the substrate results in inhibition of the downstream signaling pathways that promote leukemia.

although it inhibits the abl protein of non-cancer cells also but normal cells normally have additional tyrosine kinases which allow them to function properly.