Cracking the cancer code – the International Cancer Genome Consortium

We’re living through a revolution in cancer research. New technology is making it possible to find the genetic changes at the heart of cancer faster than ever before, unlocking the knowledge we need to save lives.

Now Cancer Research UK is taking another big step towards beating cancer by taking part in the most ambitious genetic research effort since the Human Genome Project.

Our scientists and others across the globe are working together as part of the International Cancer Genome Consortium (ICGC), building the largest ever map of the genetic faults that drive 50 different types of cancer.

The International Cancer Genome Consortium (click to enlarge)

ICGC will produce vast amounts of genetic information, and this ‘blueprint for cancer’ will fuel the search for better, more personalised treatments for the millions of people worldwide who are diagnosed with the disease every year. But how?

Understanding cancer

At the heart of every cancer you’ll find its root cause – damaged DNA. DNA is the instruction manual for our cells, and faulty DNA can make cells grow out of control and form a tumour. Luckily for researchers, a faulty instruction manual means that the story of every cancer – its strengths and its weaknesses – is written in the tumour’s DNA.

But until recently doctors haven’t been able to harness the huge potential of this information. Instead they’ve focused on the differences between the many different types of cancer, using one approach to treat breast cancer and another to treat bowel cancer.

Now we know that every cancer has its own unique ‘signature’ of genetic mutations, meaning that two people with the same type of cancer might benefit from very different treatments. The trick is to understand these signatures, and this is where ICGC comes in.

Know your enemy

We already know about the genetic changes that are important in some types of cancer, and this knowledge has brought us ‘targeted’ drugs that exploit specific faults in cancer cells.

For example, patients with a form of leukaemia called chronic myeloid leukaemia can now be tested for a specific gene fault, known as Bcr-Abl. If they carry the fault, they should benefit from treatment with the drug imatinib (Glivec) – and new data suggests that CML patients treated with this drug are effectively cured. But imatinib wouldn’t exist unless researchers had found the Bcr-Abl gene fault that it targets.

This ‘personalised’ approach is the future of cancer treatment, alongside tried and tested techniques like chemotherapy, radiotherapy and surgery.

We’re moving ever closer to being able to select a patient’s treatment based on the genetic profile of their cancer. But for this to become a reality we need to know much more about the faults that drive each type of cancer. ICGC aims to understand each of these faults in exquisite detail.

ICGC is focusing not on inherited faults, but on the genetic ‘mistakes’ that build up over a person’s lifetime.  Most cancers are caused by these ‘acquired’ faults, which determine how each tumour behaves – how it grows, spreads, and responds to treatment. Understanding these faults is the key to finding the best way to treat each patient’s cancer.

Mapping the faults at the heart of cancer

ICGC will map the genetic faults in 25,000 tumour samples from patients with 50 different types of cancer, including breast, bowel, ovarian, pancreatic and lung cancers. Cancer Research UK is leading the projects investigating prostate and oesophageal cancer.

For each type of cancer under study, the first step is to read the genetic sequences of tumour samples and healthy tissue taken from 500 patients with that cancer type.

Sequencing this much DNA is an ambitious target that has only recently become possible thanks to advances in technology. Today’s genetic sequencing machines are up to 1 million times faster than those used for the Human Genome Project ten years ago, enabling the scientists involved in ICGC to decode entire cancer genomes quickly and relatively cheaply.

The next step is more complicated. Once the DNA sequences have been decoded, researchers will compare the results of all the samples from each cancer type to find the changes they have in common.

Many of these changes are likely to have no effect on tumour growth – they’re just collateral damage caused by cells dividing out of control. The researchers’ real aim is to find the rare ‘driver’ faults that are fuelling the disease. They will compare the gene sequences from tumour samples with the equivalent sequences from the patients’ healthy tissue to help identify these key faults, which could become targets for new cancer treatments in the future.

Leading the way in oesophageal and prostate cancer

We’re proud to be leading the ICGC efforts to map the faults in oesophageal cancer, and jointly leading the prostate cancer project with cancer research organisations in Canada (the Ontario Institute of Cancer Research and Prostate Cancer Canada).

Together, prostate and oesophageal cancer are responsible for over 17,000 deaths each year in the UK alone, and we urgently need new approaches to help save more lives.

Prostate cancer

The major UK centre for the ICGC prostate cancer project is the Institute of Cancer Research in Sutton, where two of the project’s leaders – Ros Eeles and Colin Cooper – are based. Professor Eeles has an unrivalled track record in identifying genetic changes that contribute to the disease, and Professor Cooper and Cambridge-based Professor David Neal are both leading prostate cancer researchers.  Their combined expertise will ensure that this strand of ICGC makes a real difference to our understanding of the disease.

The prostate cancer team already have access to enough samples to begin sequencing immediately. They aim to start producing data by the end of the year,  and if the results are promising  they may begin to identify key genetic faults within 18 months.

ICGC will help to personalise treatment for prostate cancer by shedding light on the biology of the disease, and in the future it should help us to develop tests to predict which men need immediate treatment and which can safely avoid it.

Oesophageal cancer

Oesophageal cancer rates are rising fast in the UK, and unfortunately this type of cancer can be very difficult to treat. Our researchers are already investigating new ways to prevent, detect and treat the disease, and through our contribution to ICGC we hope to help save many more lives in the future.

Dr Rebecca Fitzgerald, a Cambridge-based expert in oesophageal cancer, will be leading Cancer Research UK’s efforts as part of ICGC.

Dr Fitzgerald and her team are still collecting tumour and blood samples. This is likely to take several years, but sequencing will start on the first samples as soon as possible. If the results are as hoped, the team can move on to larger-scale sequencing early next year – and with less than one in ten patients surviving oesophageal cancer for more than five years after diagnosis, progress is urgently needed.

Looking to the future

At Cancer Research UK we’re hugely excited by ICGC. It holds real promise for a future where personalised treatment is a reality for even more cancer patients. This huge project will uncover the faults that drive cancer, providing vital knowledge in our fight against the disease.

Armed with these new genetic discoveries, our researchers and others around the world will be able to develop more targeted treatments like imatinib, which will hit cancer where it hurts. And the information from ICGC will also give clues for new ways to prevent cancer and diagnose the disease earlier, helping even more people to live longer lives.

This is only the beginning of an exciting journey of discovery, and we’ll keep you updated on our progress over the coming months and years.

Nell Barrie

• You can find out more about ICGC on the consortium’s website.

References

Stratton, M., Campbell, P., & Futreal, P. (2009). The cancer genome Nature, 458 (7239), 719-724 DOI: 10.1038/nature07943

Stratton, M. (2011). Exploring the Genomes of Cancer Cells: Progress and Promise Science, 331 (6024), 1553-1558 DOI: 10.1126/science.1204040

Gambacorti-Passerini, C. et al (2011). Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib JNCI Journal of the National Cancer Institute, 103 (7), 553-561 DOI: 10.1093/jnci/djr060