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'A Bigger Impact'

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Just a couple of years ago, Tom Hudson was enjoying a successful and comfortable scientific career. He had established a respected genome center at McGill University in Montreal, following a post as an assistant director at the Whitehead/MIT Center for Genome Research.

But what Hudson really wanted was to "have a bigger impact" — specifically, to do work that would have direct application to patients in the clinic. As he surveyed the field, he had noticed that "the gap between what's happening in the best labs — whether it's genomics or imaging or protein assays — and what's happening in the clinic is actually getting bigger."

So when the government of Ontario came looking for a scientific director and president for its newly minted Ontario Institute for Cancer Research, Hudson jumped at the opportunity.

The institute wasn't created out of thin air. Since 2002, the Ontario Cancer Research Network had served as a way to connect groups performing clinical trials throughout the Canadian province. By late 2005, the network was doing well enough that the government decided to take the next step: creating a full institute with its own research programs. The institute was officially launched in December 2005, and in some ways maintains the legacy of the clinical trial network that was rolled into it. "My mandate is across all Ontario," says Hudson, noting that only about 40 percent of the research institute's activities take place in its downtown Toronto headquarters, while the rest are spread out in labs around the province.

When Hudson joined the institute, his first task was to figure out which research programs to establish. For six months, he embarked on "a lot of visits to cancer centers and genome centers across the world," he says. At each, he would approach people with three categories — prevention, early diagnosis, and new therapies — and ask, if they could only have one program for each, what would it be? Through that process, he says, the list came to five or six areas where there was a lot of consensus about what could be done.

Cancer stem cells became the first program. It was an obvious choice, Hudson says, since John Dick, who first discovered these stem cells, was based in Toronto. The idea of working with this particular population of stem cells also offered intriguing connections to technologies like imaging, Hudson says. "From biology we could bring in imaging — can we see the cancer stem cell populations?" The stem cell program and the imaging platform were the first two areas to get underway, he adds.

Cancer genomics was another key category. This eventually came to include the institute's participation in the International Cancer Genome Consortium; OICR's role is to map the genetic mutations involved in pancreatic cancer. Hudson, who was on the prowl for directors for each of the new programs, scored a coup when he recruited John McPherson from the Human Genome Sequencing Center at Baylor.

McPherson, who started his new post in July 2007, was the institute's first scientific hire. He says he was impressed by "the comprehensive nature of the institute that was being formed" as well as by "the very dense research environment" in Toronto.

For the cancer genomics program, "the core of that is really next-gen sequencing," McPherson says. To that end, his group has five ABI SOLiDs and five Illumina Genome Analyzers that will bear the brunt of the international consortium work. While it's still too expensive to sequence the number of samples they'll be dealing with, McPherson says he and his team will be generating data on just about everything short of full genome sequence: exome, transcriptome, epigenome, and CNVs and structural variation. While "sequencing one or two tumors won't tell you very much," McPherson says, he expects that his group will eventually choose a few representative samples and perform full genome sequencing on those.

Other research platforms at the institute include molecular pathology, medicinal chemistry, and biocomputing. Hudson says that of the 12 director-level scientists he has hired so far, half have come from Ontario and the other half have been recruited to the province. Hudson's informatics hire came as a surprise to many: Lincoln Stein, who has been at Cold Spring Harbor Laboratory for the past decade. Stein has been working part-time at the institute and at his Cold Spring Harbor lab, and while Hudson says the institute's share of time will increase, he expects that Stein will maintain his presence at CSHL in the long run.

One millimeter

What lured Hudson to the institute, and what continues to drive his vision for it, is the possibility for making a clinical impact. None of the research at the institute is just research; the entire mission, Hudson says, is to be involved in translational work that has clinical utility.

To that end, the institute has launched the One Millimeter Cancer Challenge, focused on developing technologies and approaches that will enable clinicians to see tumors as small as a millimeter, or about 100,000 to 200,000 cells. "Imaging is very strong as a discipline here," Hudson says. "There are labs which can track a single cell in an animal for six weeks. But in the clinic, we miss 100 million cells all the time."

Practically speaking, there's no reason a clinician would ever care to track a single cell. But being able to find tumors when they're just 100,000 cells would significantly increase cure rates, Hudson says. "There has to be a good fundamental technology opportunity," he adds. Scientists at the institute will be looking at new approaches to labeling, imaging, and related areas that may improve the chances of picking up these early-stage tumors.

Of course, solving that problem would create another: "Everybody's got millimeter-sized tumors," Hudson says. "We will have to learn the ideal time to treat a tumor." There may be differences in timing based on type of cancer or other attributes, he says.

Some of that will be addressed with what Hudson's calling "high-content" clinical trials — that is, trials using better technology (such as imaging) to find out sooner if something's working or not. "Can we label a drug like Herceptin and see that it actually hits the tumor as opposed to being excreted?" he wonders. That concept, with the aim of accelerating clinical trials, falls under the institute's functional pathology program.

Ontario Institute for Cancer Research
Toronto, Canada

Director: Tom Hudson
Established: 2005
Size: OICR is currently housed in one of the Mars Centre's research buildings, and will eventually move to a new building nearby when the next phase of the Mars project is completed in 2010. "We're going to be desperate for space in about a year," says John McPherson.
Staff: When Hudson joined about two years ago, there were some 20 people on staff, he says. That number is currently closer to 100, and Hudson expects to reach 250 employees in about a year and a half.
Funding: The institute's base budget is an $80 million appropriation from the Ontario government, and Hudson notes that OICR scientists still apply for grant funding through various programs as well.
Focus: Research programs at OICR target prevention, early diagnosis, and therapeutics for cancer. Technologies in the mix include genomics, imaging, pathology, high-throughput screening, informatics, and more. The institute also includes the original Ontario Cancer Research Network, which provides access to a number of facilities conducting clinical trials.

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