Scientists pinpoint protein responsible for breast cancer recurrence

Washington, June 14 (ANI): 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 tumour suppressor protein Par-4 in recurrent breast cancer.

Par-4 is down-regulated in recurrent tumours, and knocking the gene's expression down accelerates tumour recurrence in a mouse model of recurrent breast cancer. Conversely, overexpressing Par-4 delays the onset of tumour recurrence. Data from human breast cancer patients confirm these findings. The authors analysed patient tumours 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 tumour that survives chemotherapy) compared to the primary tumor prior to treatment, and that women with low Par-4 levels in their primary tumours tend to respond less well to treatment and are more likely to experience a relapse. 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.

The bottom line, Alvarez said, is that Par-4 down-regulation is both a necessary and sufficient step for breast tumour recurrence. That conclusion suggests that strategies that increase Par-4 expression in tumours could pay therapeutic dividends. In fact, turning Par-4 back on in recurrent tumour cells led to their rapid death. However, 'drugging' Par-4 won't be easy', he says.Par-4 is a tumoursuppressor protein that functions through interactions with other proteins. Neither an enzyme nor a signalling receptor, it is not a traditionally 'druggable' molecule. However, if researchers can identify the biochemical pathway that controls Par-4, or molecules that can modulate Par-4 activity directly, they may be able to increase the efficacy of neoadjuvant therapy of primary tumours as well as treat recurrent breast cancers more effectively, Alvarez said.

The team is now working on identifying pathways that regulate Par-4 levels. The findings appear in this week's issue of Cancer Cell.