New colorectal cancer target found in stem cell gene

2/12/2013

Researchers in Canada found that switching off a gene in the cancer stem cells that drive colon cancer stops them from being able to renew themselves. They say their study offers a starting point to treatments that could shut the cancer down.

Cancer stem cells are cells that have the ability to differentiate into all the types of cell that exist in that type of tumor.

Principal investigator John Dick, a senior scientist at the Princess Margaret Cancer Centre, University Health Network, Toronto, pioneered the study of cancer stem cells by identifying leukemia stem cells in 1994. He is also a Professor in the Department of Molecular Genetics, University of Toronto.

Just over a decade later, in 2007, Prof. Dick identified colon cancer stem cells. He is also known for pioneering work that isolated a pure human blood stem cell capable of regenerating the entire blood system.

He and his colleagues write about their latest discovery in a recent online issue of Nature Medicine.

First step toward clinical use of cancer stem cell biology

Prof. Dick, who also holds a Canada Research Chair in Stem Cell Biology, says:

"This is the first step toward clinically applying the principles of cancer stem cell biology to control cancer growth and advance the development of durable cures."

Senior co-author and surgeon-scientist Dr. Catherine O'Brien, also of the Princess Margaret Cancer Centre and the University of Toronto, adds:

"The clinical potential of this research is exciting because it maps a viable way to develop targeted treatment for colon cancer patients."

Colorectal cancer is the third leading cause of cancer deaths in the developed world.

For their study, the team ran a series of pre-clincal experiments where they replicated human colon cancer in mice to find out more about targeting the cancer stem cells.

They found that the gene BMI-1 - which has already been found to play a role in maintaining stem cells in other cancers - also drives self-renewal, proliferation and survival in colon cancer stem cells.

Blocking the BMI-1 pathway could shut down colon cancer

They then showed they could block the gene with a small molecule inhibitor, indicating it may be possible to develop drugs that stop colon cancer in its tracks, as Prof. Dick explains:

"When we blocked the BMI-1 pathway, the stem cells were unable to self-renew, which resulted in long-term and irreversible impairment of tumor growth. In other words, the cancer was permanently shut down."

Dr. O'Brien says it has already been shown that about 65% of colon cancer patients have the BMI-1 biomarker, adding:

"With the target identified, and a proven way to tackle it, this knowledge could readily translate into first-in-human trials to provide more personalized cancer medicine."

 

Source: Medical News Today: http://www.medicalnewstoday.com/articles/269539.php

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