What Turns a Gene On – Dr. Bonham

Dr. Bonham has always been interested in how genes are turned on and turned off, and how this process is deregulated in cancer. When he arrived in Saskatoon to begin work at the Saskatchewan Cancer Agency’s Research Unit he had just completed the cloning and characterization of the human SRC gene and was interested in how this important cancer gene appeared to be over-expressed in certain cancers.

“I think everyone is familiar with the general concept that cancer arises largely through mutation,” says Dr. Bonham. “Some genes are activated by mutation while others are inactivated. We call these oncogenes and tumour suppressor genes, respectively.”

However, some genes are over-expressed, SRC being one such example. Other genes are completely inactivated in the absence of mutations. It is this observation that has been the focus of the work in the Bonham lab for a number of years.

Originally Bonham and his team studied various aspects of SRC gene expression until an unexpected observation changed the course of the lab.

“One of my students showed that a certain drug could actually turn off the expression of the SRC gene,” he said.

This compound belonged to a class of drugs called Histone Deacetylase Inhibitors that appeared to have powerful anti-cancer activities.

“This was very exciting to us and we’ve been following this story ever since”.

At the time this observation was quite controversial and the scientific community was sceptical. “We really needed to convince people,” says Dr. Bonham. “Without local funds to get the data, it would have been very difficult.” Once the initial data was published he found it far easier to secure funds from national sources such as CIHR.

While Dr. Bonham’s past research has been mainly aimed at trying to understand how these drugs work, his more recent work has been focused on a more translational outcome. “We’ve tried to understand how these drugs reprogram gene expression and drive the cancer cell towards death and we’ve had considerable success there. However, now my lab is trying to translate this work onto something that is more directly applicable to patients.”

Working with other Agency scientists Dr. Bonham is now using state of the art approaches to look for drug combinations that might be used in the clinic. “Right now, we are using a cell-based approach to search for drug targets that work highly efficiently in combination with low doses of these Histone Deacetylase Inhibitors.” Such work promises to fast-track drug combinations relatively quickly into clinical trials.

The level of funding for cancer research remains a serious concern across the Country, with low success rates in various competitions. It is therefore vital that local funding is available to aid Saskatchewan cancer researchers. The core of cancer researchers in our province is relatively small but they are highly dedicated and producing world class, innovative work. As Dr. Bonham also points out, “I think we all would agree that we want to see the best oncologists and other specialists in our local clinics and hospitals. One way we can ensure this happens is to make sure we are providing them with a research-intensive environment because the top clinical oncologists also want to be heavily involved in research”. Supporting the new Cancer Foundation of Saskatchewan is an excellent investment to ensure this takes place.