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UCLA discovery will aid in treatment of patients with a deadly brain cancer

a, but it was not clear what characteristics made them respond to these drugs. There had to be critical molecular factors that determined response, Mischel said.

He and his team set out to find the molecular determinants that indicated which patients would respond best to EGFR blockers. Previous UCLA research in brain and other cancers suggested that the key might be the interaction of the PTEN protein and a mutant protein called EGFRvIII. About half of patients with amplified EGFR also have this mutant protein.

The UCLA team and their collaborators studied a subset of 26 glioblastoma patients who either responded very well or very poorly to EGFR blocking drugs and developed a way to test their brain tumor tissue for the presence of both the mutant and PTEN proteins. Mischel's team found that patients with both genetic variations were 51 times more likely to respond to EGFR blockers. They also lived five times longer after initiating therapy than those without the variation, surviving 253 days versus 50 days.

To confirm their promising work, Mischel and his team obtained tissue samples from 33 brain cancer patients treated at another facility without knowing who the responders were. They were able to independently replicate their results, confirming that those with both genetic variations were more likely to respond to EGFR blocking drugs.

The study shows that glioblastoma patients can respond to targeted agents, and suggests that patients likely to benefit from treatment can be identified by molecular testing. The study also raised the possibility that patients whose tumors lack the genetic variations in the molecular signature could possibly be treated with drugs to make them more sensitive to EGFR blockers.

Of the 8,000 to 10,000 glioblastoma patients diagnosed each year, about 10 to 20 percent have the combination of the mutant and PTEN proteins, Mischel said. The next step is a prospective study, determining the molecular
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Source:University of California - Los Angeles


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