Research May Lead to Improved Treatments for Cancer
January 28, 2008 - News Release
Researchers at the University of Guelph have moved a step closer to explaining why cancer drug therapies work differently in patients with the same type of tumour.
In a study published in Oncogene, one of the world's leading cancer journals, biomedical sciences professor Brenda Coomber and Siranoush Shahrzad, a senior research fellow in Coomber’s laboratory at the Ontario Veterinary College, examine the effects of anti-angiogenic therapy, which aims to block the growth of blood vessels in tumours in an attempt to stop them from growing.
Specifically, the researchers looked at the therapy's effect on mutations in the K-ras gene in colorectal cancer. The K-ras gene controls normal cell behaviour, but when it becomes altered, it's one of the most common mutations leading to aggressive and continuous tumour growth.
Previously, Coomber and Shahrzad showed that when cells have defects in their ability to repair DNA, K-ras mutations formed in hypoxic (oxygen-and nutrient-deficient) regions of tumours.
Based on those findings, they speculated that if tumours were treated with anti-angiogenic therapies, there would be an increase in the extent of hypoxic regions and in the amount of mutations in the K-ras gene.
“And that is what happened in our experimental system, which uses human tumour cells grown in mice,” said Coomber.
Her team compared untreated experimental tumours with tumours that were treated for two weeks with an anti-angiogenic agent, followed by two weeks without therapy for both groups.
During the treatment period, they found no difference between the treated and the untreated tumours. But in the two weeks after the therapy stopped, the tumours that had been treated grew rapidly.
“We found there was an increase in the amount of hypoxia and a decrease in the number of blood vessels, yet the tumours were larger and growing,” said Coomber.
“That kind of response suggests that although the anti-angiogenic approach did what it was supposed to do, it did not halt or slow the growth of the treated tumours.”
As expected, the researchers also found significantly more K-ras mutations in the treated tumours than in the untreated, but showed that the cancer drug itself did not cause the mutation.
“The outcome of this study reinforces what we already knew: responses to these anti-angiogenic approaches are not simple, and we need to look at this in many different environments and scenarios to try to understand what really might be going on," said Coomber. "It’s all about deciding what’s the best therapy for an individual patient."
She cautions that the study uses an artificial system and is focused on just one factor among many variables that influence individual responses to cancer therapy. The next step is to establish collaborations to find out whether the same thing is happening in clinical trials involving people.
“The tumour is an ecosystem and it evolves. As long as we can be aware of that, pay attention and understand it, we will be able to solve the problems this causes and the issues it raises.”
Coomber is co-director of the Institute for Comparative Cancer Investigation based at Guelph's Ontario Veterinary College. Created in 2007, it provides cancer care for companion animals and enables U of G researchers to study the disease in animals and humans alike.
“Although colorectal cancer is not a problem in the veterinary world, with certain types of cancers, we are in a position here at Guelph to look at naturally occurring tumours in animals, study their biology, try interventions and see the outcomes, then go back and re-examine our thinking about how these cancers work," she said.
"That’s how cancer therapy and research evolves, from laboratory to bedside and back again."
The research was supported by a grant from the Canadian Cancer Society.
Contact:
Brenda Coomber
Department of Biomedical Sciences
519 824-4120, Ext. 54922
bcoomber@uoguelph.ca
For media questions, contact Communications and Public Affairs: Lori Bona Hunt, 519-824-4120, Ext. 53338, l.hunt@exec.uoguelph.ca or Deirdre Healey, Ext. 56982, d.healey@exec.uoguelph.ca
