Targeted Therapies and CML

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

Glivec was the first commercially available tyrosine-kinase inhibitor for clinical use 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 specifically targeted mechanism of action and in exerting its effects on a particular abnormal protein within the leukemic cell, the Bcr-Abl tyrosine kinase.

CML was an eminent candidate disease for the rational design of a therapeutic drug aimed at a molecular pathogenetic target. The hallmark of CML, the 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 to produce an effective and well-tolerated oral CML therapy. By inhibiting only the specific cause of the disease, Glivec brought to fruition the promise of molecularly targeted CML therapy.

Work in the field of targeted therapies in CML continues with the development of the next generation of signal transduction inhibitors, including dasatinib, which was approved in 2006, and nilotinib, which was approved in 2007.

Reference

1. Druker BJ. Perspectives on the development of a molecularly targeted agent. Cancer Cell. 2002;1:31-36. [p 31, col 2, lines 13-18]

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