October 27, 2011
Decreasing specific protein in brain tumours stops growth of cancer cells: new research

Removing an overactive protein from some types of brain tumours actually stops the growth of cancer cells, CFRI’s Dr. Sandra Dunn, Dr. Catherine Pallen and Dr. Abbas Fotovati reported in Cancer Research, the most frequently cited cancer journal worldwide. Their finding opens the door to developing a drug that targets the protein called Y-box binding protein, or YB-1. The journal featured their research as its August 15 cover illustration, highlighting its potential clinical impact.

YB-1 is known to play an important role in fetal brain development. Normally, the protein turns off after birth, the researchers found in studying mice. They also discovered that YB-1 is reactivated in some brain cancers when they looked at cells from seven patients with an aggressive brain tumour called glioblastoma.

For children, brain tumours are one of the most common cause of death from cancer and glioblastoma is one of the least curable types of brain tumours.

The researchers also discovered that YB-1 is present in the brain tumour’s stem cells. These are normal brain stem cells – which typically give rise to specialized brain cells for functions such as learning and memory – that have become cancerous through a genetic mutation.

When the researchers removed YB-1 from cancer cells and cancer stem cells in the lab, both cell types stopped growing.

“Our lab studies showed that brain tumour cells need YB-1 to grow,” says Dr. Sandra Dunn, Scientist at the Child & Family Research Institute at BC Children’s Hospital and Associate Professor, Hematology and Oncology, Department of Pediatrics, University of British Columbia. “When we removed YB-1, the tumour stem cells not only stopped growing, they also regained the appearance of normal brain cells. This is a key observation as cancer stem cells are resistant to chemotherapy and radiation.”

To confirm that YB-1 is associated with cancer stem cells, the researchers analyzed tumour samples from 342 U.K. patients. YB-1 was present in cells alongside two proteins known as markers for cancer stem cells. They also found that YB-1 was present in 67 per cent of the samples from patients whose cancer had relapsed.

“Chemotherapy and radiation therapy are effective treatments for killing the bulk of tumour cells, but are not always effective at killing cancer stem cells,” says Dr. Dunn. “We believe that cancer stem cells are the source of cancer relapse.”

The next step is to find targeted drugs that shut down YB-1.

“If we can target YB-1, then we can target cancer stem cells and potentially prevent brain tumours from coming back,” says Dr. Dunn. “Targeted therapies could improve survival rates, prevent relapse and reduce some of the life-long complications of cancer treatment for children and adults. For children with glioblastoma, it could mean a better chance to live a long, healthy life.”

This research was supported by the Hannah’s Heroes Foundation, the Michael Cuccione Foundation, BC Brain Care, Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research.

[research abstract]

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Last Updated: 10/27/2011