As we celebrate the 20th anniversary of the formation of Cancer Research UK, our chief scientist Karen Vousden, contemplates the advances coming from cell biology and genomics and why the new frontiers of cancer research require a systems biology approach.
Cancer Research UK (CRUK) is celebrating its 20th anniversary. But let’s remember that we were created from two parent organisations – the Cancer Research Campaign and the Imperial Cancer Research Fund – with a much longer history of research into the causes and treatments of cancer.
Even these organisations had deeper roots; the origins of the Beatson Institute in Glasgow, for example, can be traced back to the efforts of Sir George Beatson – a far sighted surgeon who, in 1912, created an experimental research laboratory in the city’s cancer hospital.
“Over the past years many of us have woken up to the obvious – that tumours are part of a community within the host”
Decades of cancer research have brought a steady stream of improvements in diagnosis and therapy, the success of which is paralleled by an increasing understanding of this deeply complex and perplexing group of diseases. Indeed, we now realise that understanding the molecular mechanisms that cause a normal cell to become malignant and the interaction between the potentially cancerous cell and the rest of the body is a prerequisite for the development of effective treatments. If we don’t understand what’s gone wrong, it’s very difficult to do anything to try and fix things.
Chickens, genetics and the whole organism
When I started work with Professor Chris Marshall at the Institute of Cancer Research back in the 1980s, the discussion was still raging about whether cancer was truly a genetic disease.
It was known that viruses could cause cancer in chickens, but the light-bulb moment came with the realisation that the viral genes that promote tumorigenesis (so-called oncogenes) are mutated versions of normal genes that exist not only in the chicken, but also in humans. The observation pretty much laid to rest the genetic origin of cancer argument. A tsunami of research followed over the next 40 years that focused on mutations that occur within the nascent cancer cell to promote full malignant transformation.
Our laser focus on the cancer cell led to remarkable advances – targeting the EGFR/HER2 pathway or using PARP inhibitors in repair deficient cancers are some great examples. But over the past years many of us have woken up to the obvious fact that tumours are part of a community within the host. Indeed, the reaction of the rest of the body to the developing tumour is likely to give us more progress in therapy development than looking at the cancers themselves. For example, our ability to provoke the immune system into anti-tumour action has already had an unimaginable impact on the treatment of cancers like melanoma.
The next 20 years will see a continuation of this shift in focus from the cancer cells themselves towards a consideration of the whole body in cancer development. This includes not only how tumour cells interact with their local environment, but also how the tumour and whole-body systems interact. Refocusing on the patient, and not simply the cancer in isolation, will certainly increase the complexity of the research questions we need to tackle.
However, exciting programmes of investigation have already been launched that consider how the entire tumour/host system responds to carcinogens, therapies, and factors such as exercise, aging and diet.
Close to my heart is the idea that we can use an understanding of the nutrient demands of different cancers to develop precision nutritional approaches – where each patient is prescribed a bespoke diet to match them, their tumour and their therapy.
The power of mentors
I have been fortunate to have been mentored by some incredible scientists over the years, including Chris Marshall, Doug Lowy and George Vande Woude. In addition to thanking them, I’d like to thank all the senior CRUK researchers who are doing a similar outstanding job in encouraging and helping the researchers of the future. This is fantastically important work – progress for patients of the future depends on it – and is fully in line with CRUK’s ambitions to support the early career of our next generation of research stars.
Looking forward, we will see experts in areas such as metabolic disease, endocrinology, muscle physiology, neurology and cardiology brought into cancer research, greatly expanding our knowledge base and the pace of progress. But our focus will remain – success depends on our ability to understand the mechanisms that drive the genesis or treatment of cancer.
History has taught us that investment in discovery research is amply rewarded in successful development of new ways to reduce the cancer burden – which is ultimately the goal of us all at CRUK.
Karen Vousden is Cancer Research UK’s chief scientist and a group leader at the Francis Crick Institute, where her work focuses on tumour suppressors.