Dr Thomas Hudson of the International Cancer Genome Consortium Secretariat

 

 

Dr Thomas Hudson of the ICGC Secretariat, based at the Ontario Institute for Cancer Research in Toronto, tells International Innovation about the benefits of working as a large consortium in the fight against cancer

What were the some of the motivating factors underpinning the establishment of the ICGC, and what need does it address?

 

We’ve known for decades that there are a lot of mutations in cancer and that most were undiscovered; however, even 10 years ago we couldn’t define or catalogue them all because of technology and cost. These mutations are important as they can often become good diagnostic or therapeutic targets. Herceptin® is a drug that was developed to treat the 15 per cent of women with breast cancer who have an amplified gene that results in the over-expression of Human Epidermal growth factor Receptor 2 (HER2). HER2 causes breast cancer cells to reproduce in great numbers. Use of Herceptin can actually improve the prognosis of that 15 per cent of women who are HER2 positive. So the fact that there are a lot of mutations but many are prognostic markers is something that’s been intriguing: maybe there are many more to be discovered.

The ICGC’s role has been to create catalogues of all the mutations in different types of cancers across the world. We have to look at a lot of tumours but eventually we’re going to deliver many potential targets to the research community, which will be investigated for their prospective usefulness in diagnostics or therapeutics.

What strategies and approaches are you employing to build a comprehensive description of genomic changes?

 

Firstly, coordination is a key strategy. If every group were to use a different technology and use different descriptions, we may not realise, for example, that a mutation that’s driving breast cancer in some cases is also driving ovarian cancer. So we said at the outset in 2007 that we would use similar policies. We had all the cancer leaders and funders come up with principles, common rules and ethics on issues such as consent and data sharing. And we concluded that we would work together as a consortium, so even if we were developing projects in different countries, we would be coordinated, and the data we supplied to the research community would be standardised in a way that could be used most effectively.

The second strategy is technology. When we started the project we knew that technologies would continue to develop, and indeed they have done so at a rate of tenfold per year. That means that we’re already doing more than we anticipated in terms of genome analysis.

It’s a great learning experience for everyone involved. Because of these new technologies and the mixing of expertise among scientists and lawyers and agencies, there’s a high level of integration that you rarely see; we’ve all had a very rich learning experience and it has been very enjoyable.

The ICGC encompasses 50 different cancer tumour types. This is a challenging task. How does the Consortium maintain unity across such a broad range?

 

People don’t realise that cancer is a very different disease across the world. For example, there is more liver and gastric cancer in Asia, and much more breast and prostate cancer in the UK and North America; consequently, we knew it would be best to study different cancers in different parts of the world – the burden of disease is driving most of the projects. We also have two groups working on breast cancer as a ‘super project’, sharing datasets and reducing the number of samples, so the coordination has been quite easy.

We said it would take 10 years to launch all the projects, yet now we’re at 37 projects out of 50 – much faster than we anticipated. We still have gaps; we only have a few paediatric projects because of issues of consent in children, and because many paediatric cancers are rare. We don’t yet have projects in Africa or South America either, and at this point we’re working with organisations to launch projects for the disease types that are most frequent there.

In what way are you making this data available to the entire research community to accelerate research?

 

We have two levels of data; open datasets and controlled datasets. Open datasets have a cache of mutation information available, but with a very low risk of identifying individuals. This data is on a website, which the group in Toronto control. I think that we already have about 100,000 different cancer mutations on the website right now, and users can access it without restriction.

The controlled data, which also provides no name information, has information on treatment that has been received; it has genetic information – the person’s genomes, DNA, and a bit more on the drugs and exposures the patients may have had – information we believe responsible scientists know how to use and protect. It’s not information we want everyone to see, so we set up a mechanism for people to make a request for access, led by a group of lawyers in Montreal. The requests have to be justified, and institutions have to sign a contract stipulating they will make responsible use of the data, will not identify individuals and, most importantly, will not give the data to third parties. Patients who provide samples are very altruistic; they know that the research is going to take time before it’s going to have an impact, and is not likely to make any difference in their cancer management, but they also trust the researchers to take precautions, and we try to do that.

What recent achievements facilitated by the ICGC would you highlight for special attention?

 

The big advantage of being part of the ICGC is that everybody gets to learn from one another. We learned how to do ethics together, and we’re also learning how to identify mutations the same way, and how to analyse the data – this is all very new as a science. We’re sharing our knowledge and spreading solutions quickly to other groups, and that’s why funding agencies in India, China, Australia and several in Europe are very eager to participate, because it has a levering effect on just knowing how to use genomics and many other technologies.

 

Does the information you exchange assist policy makers?

In the next few months some papers are coming out on how the consortium dealt with issues of data and sample sharing, and how we overcame the legal differences. Last week we found out that the ICGC model and tools are being used by a lot of other consortiums. We make ICGC polices publicly available, and the rationale behind these policies has been the subject of several scientific articles.

What plans for the future do you have for the Consortium?

A lot of people are wondering what comes next, but we have a defined set of milestones we need to reach; goals that have to be achieved in the next decade, and we have to ensure that we deliver high quality data to the research community. It’s important the consortium keeps driving these large datasets and delivering them to the research community. Hopefully, in the future, we can look more at paediatric cancer, and also work in South America, where levels of cervical and gall-bladder cancer are very high; we also haven’t finished our task of finding funders and clinicians for all the different tumour types, but the consortium must keep on pushing.

By what means do you strive for excellence in science and scholarship, for high ethical standards in the conduct of research?

 

We have an ethical policy group that sets the standards and common guidelines across the project. We created a core set of rules that had to be adopted by the groups before they joined – such as consent forms, and letting patients know their rights. The issues of consent and legalities sometimes have different meanings in different countries. However, the application of proper ethics is the responsibility of every country. We have common guidelines, but every group has to work with a local ethics board and get permission, for example, every instance where a patient donates a tumour has to conform to a protocol approved by the hospital ethics board. The funders in each country are responsible for making these applications happen. We are actually setting precedents in terms of guidelines for some of these international issues.

 

www.icgc.org

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