Targeted Therapy
Imatinib - Glivec
Advances in the investigation of the molecular biology of cancer over several decades have made it possible to rationally design drugs to target oncogenic events with unprecedented specificity.1 One such drug, Glivec® (imatinib), has rapidly become the preferred pharmacotherapeutic option for chronic myeloid leukaemia (CML) in all stages.2,3 Glivec is the first protein-tyrosine kinase inhibitor to reach the clinic and is thus the most established molecularly targeted agent of its class. It differs from interferon alfa (IFN-α) and chemotherapeutic agents in having a well-characterised mechanism of action and in exerting its effects on a particular abnormal protein within the leukaemic cell. In clinical trials, Glivec demonstrated efficacy in CML superior to that achieved with previous systemic therapies, and it has been well tolerated by patients in all studies. The following section discusses Glivec in detail.
Chronic myeloid leukaemia is an eminent candidate disease for the rational design of a therapeutic drug aimed at a molecular pathogenetic target. The hallmark of CML, the Philadelphia (Ph) chromosome, contains the specific causative genetic abnormality that results in constitutive activation of the BCR-ABL tyrosine kinase. Glivec targets the molecular cause of CML and is an effective and well-tolerated oral therapy. By inhibiting only the specific cause of the disease, Glivec brings to fruition the promise of molecularly targeted therapy.
References:
1. Druker BJ. Perspectives on the development of a molecularly targeted agent. Cancer Cell. 2002;1:31-36.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in OncologyTM. Available at: http://www.nccn.org/professionals/. Accessed July 19, 2006
3. Peggs K, Mackinnon S. Imatinib mesylate--the new gold standard for treatment of chronic myeloid leukemia. N Engl J Med. 2003;348:1048-1050.