New colorectal cancer target found in stem cell gene

Date: Dec-02-2013Researchers 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."

He talks about their latest research in the video below.

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."

Written by Catharine Paddock PhD

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