Targeting Bcr-Abl in CML

The World Health Organization classifies chronic myeloid leukemia (CML) as a myeloproliferative disease characterized by the presence of the Ph chromosome or the Bcr-Abl fusion oncogene.¹

Advances in the investigation of the molecular biology of cancer over several decades have made it possible to rationally design drugs to target such oncogenic events with unprecedented specificity.²

The hallmark of CML, the Ph chromosome, contains the specific causative genetic abnormality that results in constitutive activation of the Bcr-Abl tyrosine kinase. CML was thus an eminent candidate disease for the rational design of a therapeutic drug aimed at a molecular pathogenetic target.

Work began in early 1990 on the discovery of Bcr-Abl inhibitors by researchers at Novartis (then Ciba-Geigy), who ultimately produced the molecularly targeted agent of its class and the first tyrosine kinase inhibitor to reach the clinic. In this new CML treatment paradigm, the specific molecular cause of CML is targeted to produce an effective and well-tolerated oral therapy.

References

1. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292-2302.
2. Druker BJ. Perspectives on the development of a molecularly targeted agent. Cancer Cell. 2002;1:31-36.

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