The New Face of Cancer

The New Face of Cancer An unusual institute is applying the newest concepts in life sciences—stem cell therapies, personalized medicine—to one of the oldest diseases. The Ontario Institute for Cancer Research (OICR) does not take a typical approach to the disease. Many cancer researchers toil away individually, only sharing their results after peer review. But for cancer researchers to receive some of the roughly $39 million the institute distributes every year, they must meet regularly with OICR program leaders to share preliminary data. They also must present their unpublished data in a closed meeting of about 300 scientists and trainees. That yearly meeting is conducted to spur new interactions and collaborations. Nor does the OICR ask the typical questions about cancer. As one of its first projects when it was formed in 2005, the OICR began to search for secrets about the ever-elusive cancer stem cells and their role in long-term tumor growth and relapse. In theory, these cells could be more important than any other cancer cells, since if they are not destroyed, they could continue to generate cancerous tissue. Led by the OICR’s John Dick, the scientist who first discovered cancer stem cells in human leukemia, the institute’s team of scientists set out to look for therapies that target the stem cells behind cancer. They also began looking for molecular markers indicating the presence of stem cells in solid tumors from breast, brain, ovaries, and other tissues. The ultimate goal: eradicate the stem cells that appear to be too difficult to treat using conventional therapy. If the program works, it could result in a new class of anti-cancer stem cell agents. But to succeed, it needs funding, and the pharmaceutical industry has traditionally been reluctant to invest in cancer stem cell research. “We need to understand cancer stem cells,” says Thomas Sellers, director of the H. Lee Moffitt Cancer Center & Research Institute, based in Tampa, Fla., where he is also executive vice president of Cancer Prevention and Control. “We need to take risks. The same old thing over the last 40 years isn’t getting it done.” As a testament to its success, the institute has already attracted industry and academic partnerships in cancer stem cell research, and awarded $80 million of funding over 4 years. The government of Ontario founded the OICR with $350 million over 5 years to build and consolidate skill in a wide range of cancer research areas. The large pot of public money has helped lower the barriers for riskier projects and is starting to fulfill the goal of innovation and translation, OICR leaders say. The OICR is a research collective of sorts. Although the institute does not do basic research, one of its priorities is to close the gap between basic findings and clinical diagnostics and therapeutics for the disease. “People don’t always pay attention to whether research leads to better clinical care or prevention, so it seems to me that what’s most impressive about OICR is the orientation toward doing science that can be translated into products,” says Sellers, who has collaborated with several of the leaders in the institute. Its in-house research center takes up 7,500 square meters within the MaRS Centre. The institute has on-site staff and leaders, and funds scientists elsewhere, based on competitive grants. Work at the OICR hub accounts for 40 percent of research activity. Here, OICR staff develop software to analyze and interpret cancer data ranging from genome sequences to population health statistics. Cancer geneticists analyze tumors for genetic mutations linked to cancer, and medicinal chemists work on discovering and developing new drugs to fight cancer. The institute has already reached capacity in the MaRS Centre, but awards grants to many scientists in the area. “Toronto is an incredible place for collaborations to take place,” says Frank Stonebanks, vice president of commercialization and chief commercial officer at the OICR. The institute has 14 next-generation sequencing platforms, and is planning to order more this year. The machines are fully occupied, sequencing DNA and RNA from 350 pancreatic cancer tumors as part of a massive—and unique in scale—effort to identify cancer-causing mutations, says John McPherson, leader of the genome technologies platform at the institute. To achieve this goal, the OICR cofounded the International Cancer Genome Consortium (ICGC), which is working on more than 25,000 tumors for more than 50 types of cancer. After validating the instruments, the group is now in the beginning stages of sequencing, and plans to mine the data to define subsets of cancers that will be more or less amenable to new therapies. “We’re quite connected with the clinical trials network, as well as medicinal chemistry and bioinformatics,” which will shorten the path to applying new cancer mutation findings, McPherson says. OICR leaders readily admit that they, and the cancer field as a whole, are far from realizing the potential of personalized medicine. Their personalized medicine initiative, which funds outside investigators through annual grant competitions, aims to develop new algorithms or software that deliver clinically useful information to health-care providers. The initiative also focuses on biomarker validation studies, preclinical validation, and clinical evaluation of new therapies. “Already with the tools we have, in a 5-year horizon, we will really improve the way molecular therapy is given to patients with cancer,” says Nicole Onetto, deputy director of the OICR, who works on the institute’s strategies and priorities. Not surprisingly, bioinformatics plays into personalized medicine and every other research strategy OICR is taking: In January, the institute announced plans to hire 40 more people in informatics this year. In the next few years, OICR plans to develop more partnerships with big pharma and establish new business models to finance late-stage clinical work taking place in academia. OICR already funds hundreds of labs that are led by Ontario-based scientists and clinical researchers, but it plans to fund 50 more in the area. “We get flooded with proposals from academic institutions all over Toronto,” Stonebanks says. To up the chances for success in the cancer field, data-sharing must occur constantly among OICR’s programs as well as between the institute and its academic and industry partners, says Frank Douglas, senior partner at Boston-based Puretech Ventures, adding that he’s “quite pleased” with the speed with which the institute came together. In the past few years, Douglas says, philanthropic cancer foundations have also been stepping up, helping move potential therapies forward by linking academic investigators with small biotech companies. “In the case of disorders like cystic fibrosis and multiple myeloma, they are de-risking the whole process by having tumor banks, sets of clinical investigators who have access to the patients, and bringing potential therapies to these expert clinicians for early study,” he adds. It remains to be seen whether the OICR’s plan and structure will ultimately generate innovative therapeutics or diagnostics. It’s so new, Sellers says, that it might be too soon to measure its progress through, for example, products, patents and publications. “It’s unrealistic to expect that an organization that’s 4 or 5 years old is going to have much in the way of new patents and new discovery,” Sellers says. “What’s going to accelerate them in this case is that the faculty are very accomplished, and that bodes well.” Facts From fiscal year 2008 to 2009, OICR-funded PIs were awarded $40.6 million in outside grants. OICR’s programs and platforms published 150 papers in a 2-year period ending March 31, 2009, and at least several dozen more since, not including the outside research projects the institute funds. The largest gene-sequencing project in history, the ICGC, will complete DNA sequencing equivalent to 25,000 Human Genome Projects in an effort to identify cancer-linked mutations for 50 of the most common types of cancer. The OICR awarded $39 million in research funds to off-site scientists from 2009 to 2010. The OICR has established major partnerships with public organizations such as the Terry Fox Research Institute and Cancer Care Ontario and with companies such as Pfizer and General Electric Health Care. Such partnerships have generated more than $100 million to support OICR programs based in Ontario. OICR investigators have hundreds of promising early stage discoveries in the pipeline.

The New Face of Cancer

The New Face of Cancer

An unusual institute is applying the newest concepts in life sciences—stem cell therapies, personalized medicine—to one of the oldest diseases.

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Kelly Rae Chi

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December 2010

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