Abstract
Imatinib mesylate (IM), a tyrosine kinase inhibitor, is one of the first molecularly targeted therapies to have been used in the clinic. It has proven to be efficient in the treatment of chronic myeloid leukemia and also in other malignancies that involve expression of a tyrosine kinase. However, some patients can develop resistance and others suffer from toxic side effects. The pharmacokinetics of IM depends on several enzymes and transporters, and several studies have attempted to identify genetic factors associated with variable drug levels and clinical responses using a candidate gene approach. Larger and more homogenous studies are still needed to replicate the findings obtained so far, or to analyze other genetic variations to get clearer insights into how IM treatment can be tailored to each patient's genetics. Here we summarize pharmacogenetic studies of IM and highlight the genetic markers that could be used to improve the treatment and management of diseases for which IM is used.
Highlights
Imatinib mesylate (IM, known as STI571, Glivec or Gleevec) is a competitive tyrosine kinase inhibitor commonly used for treatment of chronic myeloid leukemia (CML)
In CML, IM inhibits the tyrosine kinase activity of the fusion protein of breakpoint cluster region (BCR) gene and the ABL tyrosine kinase (BCRABL), which results from a t(9;22)(q34,q11) translocation known as the Philadelphia chromosome; this fusion
Concluding remarks Despite several groups attempting to demonstrate the impact of candidate gene polymorphisms, conflicting results remain
Summary
Imatinib mesylate (IM, known as STI571, Glivec or Gleevec) is a competitive tyrosine kinase inhibitor commonly used for treatment of chronic myeloid leukemia (CML). It has proven efficient for the treatment of advanced gastrointestinal stromal tumors (GISTs), c-KIT mastocytosis and myeloproliferative disorders with rearrangement of the platelet derived growth factor receptor (PDGFR) gene. Three main criteria can be used to evaluate the response to CML treatment: complete hematological remission, defined as a normal peripheral blood count with normal spleen; complete cytogenetic response (CCyR), defined by absence of the Philadelphia chromosome in bone marrow metaphase analysis; and major molecular response (MMR), defined by the thousandfold (3 log) reduction in BCR-ABL transcript levels relative to the standardized baseline [1].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
