Molecular testing in patients with rare cancer predicts response ...( ical response to Gleevec among patients...),Health

"We are pleased that the findings in this study substantiate our earlier observations," said Christopher L. Corless, M.D., Ph.D., who collaborated with Heinrich on the study. "Molecular subtyping of GIST is clearly important to understanding how Gleevec and other drugs in the pipeline affect growth signaling in these tumors." Corless is a professor of pathology in the OHSU School of Medicine and PVAMC and a member of the OHSU Cancer Institute.

Researchers analyzed tumor DNA samples from 324 GIST patients, obtained before they began treatment with Gleevec, and correlated the findings with subsequent patient outcome. Of 280 tumors with abnormalities of the KIT gene, those with a mutation in a segment called "exon 11" were significantly more likely to have a clinical response to Gleevec than patients whose tumor had a KIT "exon 9" mutation or had no mutations. Patients with the KIT exon 11 mutation responded to Gleevec for a longer period (576 days) than those with the KIT exon 9 mutation (308 days).

"However, there was no difference in the likelihood of clinical response between the two doses used in the study," said Heinrich. "The presence of an exon 11 type mutation was the single best predictor of clinical response to Gleevec, irrespective of dose."

The study also confirmed that new drugs are urgently needed for patients whose GIST genotype is less responsive to Gleevec. In response to this clinical need, future studies planned by Heinrich and colleagues will evaluate the use of Gleevec in combination with other agents to treat GIST patients.

"We have a powerful tool in Gleevec," said Heinrich. "However, we need t
'"/>

Contact: Rachel MacKnight
macknigh@ohsu.edu
503-494-8231
Oregon Health & Science University
15-May-2005