enaBling technologies

Enabling better diagnosis and treatments for cancer patients

“THE BIG C”

Cancer is the leading cause of death in Canada: just over two in fi ve Canadians will develop some form of cancer in their lifetime, and one in four Canadians will die from it. Last year alone some 187,600 Canadians were diagnosed with cancer, and there were 75,500 cancer deaths. Canada ranks 12th in the world for cancer frequency.

More than half of new cancer cases diagnosed this year will be lung, breast, colorectal and prostate cancer. Lung cancer is by far the leading cause of cancer death, leading to more cancer deaths among Canadians than the other three cancers combined. Overall cancer rates are slowly dropping, but the numbers are still frightening. There’s a reason why it’s known as “The Big C”.

However there is hope on the horizon. Genomics, already showing promise in other fi elds of medicine, is now being applied in cancer diagnosis, treatment and care.

Personalized cancer treatment

In the not so distant future, the genomes of cancer tumours will routinely be sequenced as part of the clinical evaluation of cancer patients, helping usher in the much-anticipated era of ‘personalized’ treatment. In certain instances of cancer such as hereditary breast cancer, cancer cell sequencing already occurs. Oncologists use this information to tailor treatments that will respond to the unique makeup of the patient’s tumour genes.

The technologies driving the genomic breakthroughs of the last 15 years are making genomics a powerful, integral and necessary part of cancer screening and treatment. Canada is helping to lead the way in developing these technologies, with home-grown innovators who are poised to take the world by storm.

Necessity is the mother of entrepreneurship

In 2002, a technology development platform funded by Genome BC and Genome Canada was created in BC to provide engineering support to the local life sciences research community along with world-class prototyping facilities and resources for advancing innovative biomedical devices towards commercialization. In 2007, with support from Western Economic Diversifi cation Canada, Genome BC secured funding for advanced prototyping facilities and training centres in BC. The funding established new facilities at the UVicGenome BC Proteomics Centre and the British Columbia Institute of Technology. It also launched the Joint Engineering Centre, a stateof-the-art prototyping centre at the BC Cancer Agency.

The close proximity of the teams’ engineers and trainees to researchers and clinicians in the local research community is one of the keys of the platform’s success. Through close interaction and networking, researchers have been able to identify ways to solve problems, improve effi ciencies and invent new devices.

Platform members have created dozens of technologies including devices for high-throughput genome analysis with the BC Cancer Agency’s Michael Smith Genome Sciences Centre, the design of devices for radiotherapy and clinical genetics at the BC Cancer Agency, anesthesiology devices for Vancouver General Hospital and work fl ow improvements for the BC Centre for Disease Control, among many other innovative projects.

Enabling non-invasive cancer monitoring

One of the major successes of Genome BC’s Technology Development platform is Boreal Genomics, a spin-off company started in 2007 by co-director and UBC researcher Dr. Andre Marziali and colleagues. In 2004 Dr. Marziali co-invented a patented technol-

UBC researcher Dr. Andre Marziali

ogy to purify nucleic acids. This technology formed the basis of Boreal to further commercialize high-performance instruments for DNA and RNA purification. The company’s newest product, the Boreal OnTarget™ platform, allows researchers to detect up to 100 mutations across multiple genes in parallel and sequence both known rare somatic mutations, enabling non-invasive monitoring of cancer and improving the effectiveness of personalized treatments. The OnTarget platform enables multiple detection of these mutations from circulating tumour DNA in plasma.

The initial commercial application for the OnTarget system is for colorectal cancer surveillance but Boreal has also developed applications in detection of pancreatic, ovarian and lung cancers. The market for colorectal monitoring in North America is over two million tests annually, with similar population based numbers seen internationally. Factor in other cancers to the screening panel and the numbers are significant. The brilliance of the technology, however, is its potential to detect all cancers at even the earliest stages, and all with a simple blood test.

With a recent $18 million (USD) injection from a Series C financing round, Boreal has the ability to improve cancer patient care through blood-based tests for non-invasive tumour profiling. It aims to further develop its cancer-detection platform from post-surgical surveillance for circulating cancer DNA into a screening tool that can be applied across entire populations, eventually hoping to decrease the global incidence of late-stage tumours. With clinical applications underway and cancer detection data on the verge of publication this technology is quickly becoming the “holy grail” of cancer treatment.

The recent round of funding will also be used to expand the company’s commercial operations in the translational research market and launch clinical applications for non-invasive genomic profiling and monitoring of cancer.

MAGIC is for real

In addition to novel innovations like OnTarget, some cancer diagnosis systems have already been advanced significantly through DNA sequencing technologies for cancer. One of the best examples of this can be seen in work being done by the Medulloblastoma Advanced Genomics International Consortium (MAGIC). In partnership with clinicians at The Hospital for Sick Children (SickKids) in Ontario and 46 cancer centres around the world, scientists at the BC Cancer Agency’s Michael Smith Genome Sciences Centre (GSC) are obtaining a DNA-level understanding of medulloblastoma, the most common form of childhood cancer.

The children who survive the aggressive and debilitating treatments must often then cope with a host of side-effects, such as learning challenges and physical disabilities. There is also a major challenge in deciding what additional treatment to go with to avoid recurrence knowing that radiation treatment leads to permanent cognitive impairment.

In essence, saving the child’s life is an important initial victory, but also the start of life-long challenges for the child, their family and the health care system. Studies indicate that children are often overtreated because presently there is no way to predict which patients need which additional therapies such as radiation and chemo. If there were a test that could predict which therapies are needed to prevent recurrence of the tumour, these kids could be spared complications by reducing the types and quantities of treatments they receive. At the same time, children with a poor prognosis are often subjected to painful treatments that may in fact, be futile. The tricky part is to identify which children are being over-treated and could be spared some of the side effects of treatment.

Sequence, Stratify, Save

For the past few years researchers on the MAGIC project at the GSC have conducted RNA, micro RNA and DNA sequencing for over 1,000 tissue samples obtained from children around the world who have had medulloblastoma. Armed with this analysis the MAGIC team is basing its work around the understanding that medulloblastoma can be stratified into four distinct subgroups, each of which has a different prognosis when treated with chemotherapy, radiation and drug therapy. The team has managed to determine that two of the subgroups, simply named Groups 3 and 4 have the worst prognosis while the other two Groups, 1 and 2, have a generally good prognosis and don’t require radiation but can be treated with surgery and chemotherapy thus minimizing the lifelong cognitive impacts caused by radiation.

The team’s research has focused on the molecular makeup of medulloblastoma cancer, specifically the identification of relevant genomic changes. The team has also discovered somatic copy number aberrations in each of the four subgroups. For instance, in Group 4 a gene associated with Parkinson’s disease is duplicated and in Group 3 another gene is translocated. These events are significant, and scientists’ understanding of them offers potential treatment targets for patients classified in those groups.

To identify subgroup-specific therapies, the team is concentrating on identifying subgroup-specific drug targets, especially for those two groups with the worst prognosis. Currently the MAGIC team has identified potential drug targets specific to Group 3 medulloblastoma patients – patients who are facing the worst prognosis. Tumour samples from Group 2 have also been analyzed and variations in DNA makeup identified will help with treatment as well. Tumour samples from Group 1 identified no changes in the DNA and typically have very good outcomes to treatment and a healthier prognosis. Research from the MAGIC project is transforming the way that children with medulloblastoma are treated.

A wonderful collision of worlds

Significant investments in cancer genomics projects are leading to a more personalized and cost- effective approach to cancer diagnosis and treatment — and better outcomes for patients and their families. The incredible advances in technology happening almost daily are moving from the bench to bedside to making genuinely better and more informed clinical decisions and improve patient care.

The future of cancer diagnosis and treatment is much, much brighter than it has been before. For this we can thank the brilliant innovators who are not satisfied with the status quo and push for change, the far-sighted government bodies who invest in research teams and the people behind enabling technologies who bring reality to ideas.

To see this story online visit http://biotechnologyfocus.ca/enabling-technologiesenabling-better-diagnosis-and-treatments-for-cancerpatients