Out of the Shadows

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By Kristine Archer

It may be an old cliché, but it endures for a reason — an ounce of prevention may, in fact, be worth much more than a pound of cure.
But you cannot prevent what you cannot detect, which is where researchers at the BC Cancer Agency (Vancouver, BC) come into the picture. Located in a province with a long history of successful cancer screening programs, the BC Cancer Agency plays host to a wide breadth of investigators committed to early cancer detection.
Calum MacAulay, PhD, who heads the agency’s cancer imaging department, is one of those researchers interested in bringing the early signs of cancer into focus.

A New Lease on LIFE
MacAulay, a clinical associate professor in pathology and laboratory medicine at the University of British Columbia (UBC) (Vancouver, BC), says academic background plays a large part in how he and his team approach the complex issue of cancer.
“Our department is mostly physicists and engineers, so we didn’t come with the background in biology,” he explains. “When I look at it (in terms of) the big picture, it just makes much more sense to attack it early than to wait until it’s a real problem.”
While most people think of the proverbial miracle drug when cancer research is called to mind, MacAulay has chosen to focus on one of the most surefire ways of successfully treating the deadly disease — finding it as early as possible.
With that in mind, MacAulay and his colleagues developed the Light Induced Fluorescence Endoscope (LIFE), which enables a more than two-times improvement in detecting lung cancer in its earliest stages.
“The LIFE device, and most of the fluorescence devices we use, uses blue light. We are using that to excite fluorescence in tissue,” he says. “The blue light penetrates into the tissue, it gets scattered by the epithelium and most of it gets absorbed. But some of the light that gets absorbed will be re-emitted as fluorescence.
“What we’ve sort of stumbled upon is that normal tissue will fluoresce quite strongly in the green,” he adds, “and abnormal tissue — certainly in the lungs anyway — is much darker: it has a sort of reddish-brown colour.”
MacAulay continues, “As you get abnormal tissue — as it starts to turn towards becoming cancer — the epithelium gets a little bit thicker.
“What happens is the light that you’re shining on the surface goes through the epithelium but that epithelium’s getting thicker . . . and increased scattering in the thicker epithelium means that whatever green light is actually generated down there has less of a chance of getting out. The red light, which travels further through tissue, actually does get out so it makes it turn slightly red.
“It becomes fairly straightforward to see, at least in the lung,” he concludes. “It’s two to six times more sensitive than just doing it by eye.”
The LIFE device, MacAulay says, offers a solution to a common issue facing early detection.
“One of the problems was that the pathologist had generally not seen these lesions ever before, because no one could find them,” he explains. “There was a whole training issue that came up for the pathologist because no technology existed before this to actually find these lesions in the lung with any degree of reliability.”
With so many types of cancer to focus on, MacAulay says the choice to concentrate on lung cancer was simply a matter of numbers.
“Lung cancer is the major cancer killer for men and now for women,” he says. “If you take the next three worst cancers, they’re still not as bad as lung cancer is by itself.”
According to MacAulay, the advantage of the LIFE technology is that it can be applied to other types of cancer.
“We’re currently working on projects where we’re trying to apply this technology, and versions of this technology, to cervical cancer screening and detection, as well as oral cancer screening and detection, and skin cancer screening, detection and localization.”
MacAulay points to oral cancer as the most promising secondary indication, which is where his colleague, Miriam Rosin, PhD, enters the picture.

Putting Her Money Where Your Mouth Is
Rosin had been studying the implementation of disease screening and prevention long before coming to the BC Cancer Agency. She spent several years traveling the world, from India to Russia to Taiwan, “looking at strategies for developing biomarkers that would let us know whether a person was at risk for developing cancer and then looking at intervention,” she explains.
“It wasn’t enough to have lab models,” she says. “If we were going to have an impact on disease, we needed to be following (it) inside of people and intervening.”
Rosin, a professor at UBC and Burnaby, B.C.-based Simon Fraser University, now works with the British Columbia Oral Cancer Prevention Program (BCOCPP), which was initiated through a series of grants from the U.S. National Institutes of Health (NIH), specifically the National Institute of Dental Craniofacial Research.
“Oral cancer is really a devastating disease,” Rosin explains. “The intervention is usually surgery, if you catch it early enough. If not, it’s surgery and radiation (and) you can imagine if you go in there and you start chopping away it affects the way you talk and the way you eat. And if its spread widely, it’s disfiguring.”
The BCOCPP is distinctive because of its amalgamated approach to tackling a complex problem.
“What’s going to make B.C. totally unique is this intense integration of people who have a common vision,” Rosin says. “And that vision is to do something about this disease, and to do it at an early stage.”
Two different visualization techniques have been launched by Rosin’s group. In September 2005, a study published in Cancer Research showed that lesions that absorbed the dye toluidine blue were six times more likely to become oral cancers.
“We have a core of 400 patients inside of the Cancer Agency that we are following over time, looking to see if we can predict whether or not they’ll develop cancer by identifying changes,” Rosin explains. “In that case, we found that if you painted this dye on an early change — this is before cancer — and the dye was retained, there was six times the chance of (the change) developing into a tumour in the future.”
Two months later, the BCOCPP received a $2.5-million grant from the NIH to further research into the VELScope, a portable instrument that, in a similar manner to the LIFE device, helps dentists define the borders of an otherwise-invisible cancerous lesion in the mouth.
“This is really exciting for us. What we’re looking at here is a simple hand-held tool that shines inside the mouth,” Rosin explains, noting that the device would allow dentists to refer high-risk patients for a biopsy or further treatment. The VELScope is currently being used in a clinical trial at the Cancer Agency, and will be soon used on high-risk patient groups in dentists’ offices across the province.

Taking the Next Step
A new tool of this kind is useless, however, without the proper training.
“It’s no good for us to just create a knowledge base or create the devices if we can’t transfer them,” Rosin says. “Right up front, with all of our partnerships, there’s an understanding that knowledge transference is key.”

Rosin points to an educational program, developed in collaboration with the BC Dental Association and UBC’s faculty of dentistry, as one of the crucial aspects of the VELScope project.
“We’re very, very excited about it, because now you’re talking about groups of these disciplines that are coming to the table,” Rosin explains. “It’s an incredibly bold integration of different people with different abilities, and the goal is to maximize those partnerships.
“The issue is: how do you form a partnership with the community? How do you link a surgeon who’s very busy, with a research scientist who usually doesn’t leave the lab, and then link them to a dentist who’s managing his patients, and still make it workable?” she adds.
“It means that you have to have very dedicated people across all the disciplines trying to figure out how they can put those pieces together and make it functional,” Rosin continues. She points to this as a reason why the BCOCPP has attracted three grants from the U.S., an uncommon feat for a single Canadian program.
“In the U.S., if you go to any of the big cancer centres, they don’t have a direct partnership with community,” Rosin says. “The partnership will come if you can prove you can do it. That’s why the NIH is really excited about what we’re doing.”
The key, Rosin says, is setting the example and showing what is possible in order to facilitate adoption of this type of program.
“(As) we show that the dentist can actually detect early disease with (these tools), and we show that we can actually improve outcome, then it will become a proof of principle and it will force change.”

Making Progress
Both MacAulay and Rosin say research focusing on early detection methods has become more prevalent in recent years, which is a welcome change.
“My personal opinion is that we — the research community — have spent a lot of time and effort on the treatment of advanced cancers and, in my opinion, not enough on the early detection,” MacAulay says.
“I think that more effort needs to be expended in the area of early detection and diagnosis,” he adds. “And actually, I would have to say, in the last three or four years, it appears to me that more people are paying attention to that.”
It is ultimately the desire to affect change that drives Rosin and her colleagues.
“Everybody inside of the program, they have that vision,” she says. “They’re tired of not being able to change things, and they basically want to say ‘This is our goal, this is what we’re going to do and we’re going to do it’.”