The GIST of the matter

Phase II data on a new indication for Novartis AG's Gleevec, presented at the American Society of Clinical Oncology meeting last week, provide a good example of the value of understanding the molecular mechanisms behind cancer. It turns out that Gleevec acts not only on the kinase that is over-expressed in chronic myeloid leukemia (CML), for which Gleevec was just approved, but also on one that plays a role in gastrointestinal stromal tumors (GIST).

Gleevec selectively inhibits just three of the many tyrosine kinases: Abl, Kit and platelet derived growth factor receptor (PDGFr). In CML, patients have a mutant protein, Bcr-Abl, which is created when part of the bcr gene on chromosome 9 is fused with the Abl kinase on chromosome 22. In the fusion protein, the Abl kinase is permanently activated, causing CML. Although the reason for elevated Bcr-Abl activity isn't known, it is clear that elevated activity of the enzyme causes the malignancy...