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Novel biomarker may predict response to new VEGF receptor inhibitor
Date:9/28/2010

scovered in our animal models may be replicated in human tumors, and may be an important discovery relevant to patient care," said Robinson.

At the AACR conference, Robinson showed that the same biomarker identified in AVEO's breast tumor model was associated with clinical activity in a set of kidney tumor patients from a previous Phase II kidney cancer trial. This biomarker is associated with white blood immune cells that are recruited into the tumor to produce angiogenic growth factors.

"This produces an intrinsic resistance to tivozanib, which is an anti-angiogenesis agent," Robinson said.

The researchers inserted specific oncogenes and other engineered genes altered in numerous cancer types into the tissue of animals and then studied the variety of tumors that were produced. For example, genetically altering the HER2 gene resulted in tumors that naturally expressed different pathways for growth, Robinson said.

"That mimics what happens in women with HER2-positive breast cancer because across patients, there is a significant variation in these HER2 tumors that dramatically alters their response to treatment," he said.

After molecularly characterizing each tumor, they tested what happened when the cancer was treated.

"Because we have the molecular character of the tumor, we can associate biology with response. We have an ongoing effort to discover and develop predictive biomarkers that will aid our clinical development strategies and, we believe, maximize the benefit for specific patient populations," Robinson said.

In this way the researchers isolated tumors that do not respond to tivozanib, and from this they were able to identify the resistant biological phenotype. Further study revealed a correlation between the biomarkers and tivozanib clinical activity.


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Contact: Jeremy Moore
jeremy.moore@aacr.org
267-646-0557
American Association for Cancer Research
Source:Eurekalert

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