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Protein protects against breast cancer recurrence in animal model
Date:6/13/2013

PHILADELPHIA - According to the American Cancer Society, nearly 40,000 women in the United States will succumb to breast cancer this year. Most of these women will die not from the primary tumor but rather tumor recurrence the reappearance of the disease following treatment.

Precisely what causes breast cancer recurrence has been poorly understood. But now a piece of the puzzle has fallen into place: Researchers at the Perelman School of Medicine, University of Pennsylvania have identified a key molecular player in recurrent breast cancer a finding that suggests potential new therapeutic strategies.

The study, performed in the laboratory of Lewis A. Chodosh MD, PhD, chair of Cancer Biology and director of Cancer Genetics at the Abramson Family Cancer Research Institute, implicates the tumor suppressor protein Par-4 in recurrent breast cancer.

Par-4 is downregulated in recurrent tumors, and knocking the gene's expression down accelerates tumor recurrence in a mouse model of recurrent breast cancer. Conversely, overexpressing Par-4 delays the onset of tumor recurrence.

Data from human breast cancer patients confirm these findings. The authors analyzed patient tumors from the I-SPY 1 TRIAL, a clinical trial that measured tumor gene expression patterns and response to neoadjuvant chemotherapy. They found that Par-4 expression is low in "residual disease" (that portion of a tumor that survives chemotherapy) compared to the primary tumor prior to treatment, and that women with low Par-4 levels in their primary tumors tend to respond less well to treatment and are more likely to experience a relapse.

The findings appear in this week's issue of Cancer Cell.

The study was led by Chodosh senior postdoctoral fellow, James V. Alvarez, PhD. Alvarez and his colleagues teased apart the role of Par-4 using a mouse model of recurrent breast cancer. In this model, turning "on" the HER2/neu oncogene in mice -- whi
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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