Last month the US Food and Drug Administration (FDA) approved STI571 for the treatment of chronic myeloid leukemia (CML). Although Phase III clinical trials are not complete, meaning that the long-term efficacy and safety profile of the drug is not yet determined, the preliminary results from Phase I and II trials were so encouraging that the manufacturer, Novartis, applied for a fast-track review last February. The FDA should be applauded for its alacrity, enabling a highly promising cancer drug to become available much sooner to patients.

CML is a rare form of leukemia affecting 4,500 people in the US each year. It is a clonal hematopoietic stem-cell disorder characterized by the Philadelphia chromosome, the result of a balanced translocation between chromosomes 9 and 22. This translocation leads to a gene fusion the product of which, BCR-ABL, is constitutively 'on' and activates a number of signal transduction pathways involved in cell proliferation and apoptosis, leading to myeloid proliferation.

CML is a particularly good disease target since it is one of the few malignancies that can be ascribed to an underlying defect in a single molecule. STI571 specifically inhibits ABL1 protein tyrosine kinase, and these results elegantly illustrate the power of research founded on a good understanding of the underlying mechanisms of biological action. In addition, STI571 blocks autophosphorylation of the Kit and PDGF receptors, and the drug is now in clinical trials for cancers in which these kinases are activated, such as gastrointestinal stromal tumors, some gliomas and tissue sarcomas.

Of course, it's not all good news. Although STI571 therapy has yielded impressive results for patients in the chronic phase of CML, the drug is not effective in the acute phase and long-term treatment has led to the development of drug-resistant tumors. Combination therapies are now being developed that may circumvent these problems.

Nevertheless, STI571 is one of over 16 new kinase inhibitors that are now in development and its success offers real hope that molecular targeted therapy is finally becoming a reality.