British Science Week: 10 of the biggest changes in cancer research over the last 20 years

This year’s British Science Week runs from 10^th–19^th March, and the theme is ‘change’.

We asked 10 of our experts across a range of areas to tell us how they think their field has changed over the last 20 years, and what might be on the horizon.

Cancer research – Professor Karen Vousden, our chief scientist

In recent years I think research has really hammered home just how complicated cancer can be. We’re now beginning to understand that each individual tumour is different. And we’re starting to appreciate just how diverse cancers can be between patients, even those that develop in the same tissues and organs within the body.

The cost of doing challenging technological things like reading a cell’s entire DNA sequence, or monitoring the proteins and molecules it produces, has plummeted. And this has allowed scientists to ask bigger questions than ever before.

We can now more closely follow the genetic changes that fuel a cancer’s growth. And we can do that with many more samples than we could previously, allowing us to begin piecing together the complexity of cancer.

On top of this, exciting new ways of editing a cell’s DNA in the lab have made it possible to precisely test how gene faults we might see in a patient affect the way a cell behaves.

And this can then all be analysed and interpreted together thanks to better ways of handling the ‘Big Data’ that this type of research produces.

For many years now my own lab, along with colleagues at the Beatson Institute, have been studying how cancer cells feed themselves, and how they make all the complex building blocks that are needed to make more cancer cells. And I think these processes, collectively called cancer metabolism, will become particularly important over the next few years.

We’re finding that this is another area where the world around tumour cells – what’s known as the tumour microenvironment – could have a big part to play too.

And I think this appreciation of cancer being not just rogue cells, but an entire rogue system of different cells and molecules, will become one of the biggest focuses in research.

Immunotherapy – Professor Adrian Hayday, Immunosurveillance Laboratory group leader at the Francis Crick Institute

One of the most dramatic changes in cancer biology this century has been in the field of immunology. The immune system can detect potentially harmful bacteria and viruses as a threat and eradicate them, potentially giving us lifelong protection against these invaders. Perhaps wishfully, it was considered that the immune system would be able to recognise cancers as a threat and attack them, maybe even preventing them from reappearing in the future. But up until 2001, studies failed to show that people with weakened immune systems were more susceptible to cancer, causing cancer immunology to fall off the radar.

Since then, several dramatic observations have been made. For example our laboratory discovered that animals lacking very specific components of the immune system were more susceptible to cancer, and this has now been taken forward into a treatment approach.

This and many other studies made it clear that the immune system can often recognise cancers, but that its activity is usually dampened by ‘brakes’, called “checkpoints” that naturally operate to prevent the immune system from going into overdrive. Inevitably, investigators then wondered what might happen if those checkpoints were blocked. Remarkably, several such checkpoint inhibitors have achieved cure rates of around 30% or more in patients with late-stage melanoma and lung cancer that had no treatment options left. This has been a sea-change in cancer treatment and in how we think about cancer immunology.

There are many questions left to answer. Why do some people’s immune systems not recognise their cancers? Why do some tumours fail to respond to checkpoint inhibitors? And why do checkpoint inhibitors not work at all well in some cancers? Although there is much to learn, and much to improve, immunotherapy is here to stay – a massive and hugely optimistic change since the year 2000.

Early diagnosis – Professor Willie Hamilton, professor of primary care diagnostics at the University of Exeter

Change is the one constant in life. I’ve just googled that and was disappointed Heraclitus beat me to it by 2,500 years, unfortunately.

We’ve seen dramatic changes in NHS cancer diagnostics in the last 15 years, following a clear scientific and political recognition in the late 1990s that lives were being lost. Each of the main parties and their governments has appreciated the need for change.

One of the key steps was the introduction of 2-week clinics, promising patients that they would be seen within that time. It probably wasn’t the specific timeframe that has been important but the recognition that solid, reliable clinical pathways have to be in place. These clinics have increased in use and have been a success.

Coupled with this have been two very influential NICE guidance documents, the first in 2005 which was revised in 2015. These really catalysed change by describing the patterns of symptoms that represent a reasonable chance of cancer.

I think the ‘next big thing’ will be reliable blood tests for a range of common cancers, allowing GPs to do reasonably accurate, and quick, testing.

Has the current approach worked? Well, the time taken to diagnose cancer has fallen over the last decade, a smaller proportion of cancer patients are presenting as an emergency (this really matters, as the complications of cancer can kill) and survival is improving.

Are these all connected? Is this an NHS success? Probably – and I reckon Heraclitus would agree.

Behavioural Science – Professor Robert West, CRUK expert in health psychology at University College London

The last 20 years has witnessed a quiet revolution in the role of behavioural science for combating cancer. The evidence on behaviour as a cause of cancer has piled up. Smoking and UV exposure is top of the list, but more recently we’ve realised that alcohol consumption, physical activity, diet and infections also play a crucial role in cancer development.

There’s also been a huge advance in our understanding of behaviour and how to support people to take control of their lives and preserve their health. We now know that this support goes far beyond what some may see as just ‘common sense’.

Over the years, scientists have also developed techniques that are proven to improve the chance of people changing their behaviour.

But there’s more to come. Artificial Intelligence and machine learning are now being used to create and test changes in behaviour to answer the big questions of what works; for which behaviours; for whom; in what setting; and why? Watch this space!

 

Imaging – Dr Ferdia Gallagher, Honorary Consultant Radiologist at the Cancer Research UK Cambridge Centre

Medical imaging has rapidly evolved over the last 40 years. The field of radiology was born in the late 19th century with the discovery of X-rays but developed little until the 1970s, when new techniques moved imaging from 2 dimensions into 3 dimensions. This significantly increased our ability to detect tumours and, since then, medical imaging has grown rapidly.

In the field of Magnetic Resonance Imaging (MRI), the technology has progressed from the very first image published in 1973 of two tubes of water, to the detailed scans of patients we are familiar with today. We can now give patients contrast agents with both MRI and Computed Tomography (CT) that allow us to observe changes in blood flow that occur as a consequence of tumour growth. CT scanners can now image the whole body using much less radiation compared to 15 years ago, reducing the risk to patients.

In the future, imaging will continue to become more specific, moving away from imaging anatomy alone to probing specific biological processes. For example, rather than waiting to see a tumour shrink in response to treatment, we can now image its energy consumption and tell if it is responding to a drug much earlier. In this way, a patient’s chemotherapy can be tailored towards their specific needs, sometimes termed personalised medicine. This could save the NHS money because treatments that are not working would be stopped earlier.

Another way in which imaging will change is through combining diagnostic imaging with therapy. For example imaging could help direct a drug or radiotherapy towards a tumour much more accurately, concentrating the treatment where it is needed. Imaging has several advantages over other diagnostic techniques, such as being non-invasive and allowing us to repeatedly image the patient over time.

 

Radiotherapy – Professor Corrine Faivre-Finn, Cancer Research UK radiotherapy expert at the Christie Hospital in Manchester

Radiotherapy has changed enormously – from quite rudimental treatments that affected large areas of the body, to today’s more precise techniques that spare healthy tissue. Equipment used to be fairly inaccurate, which would cause side effects and risk giving too low dose to the tumour, but improvements to machinery have reduced this significantly.

In the future there will be a lot more advances with modern radiotherapy machines. These are all designed to be highly focused and give a direct hit of radiotherapy to the tumour, while sparing healthy tissue. There’s also a lot of excitement around using immunotherapies alongside radiotherapy.

In fact, Cancer Research UK trials are being set up as we speak to see if immunotherapy boosts the effects of radiotherapy. This will be an interesting development that we might see in the next few years.

Hopefully in the next 20 years, radiotherapy is going to be so precise that in some diseases it may replace surgery altogether.

Precision medicine – Professor Peter Johnson, director of our Southampton Cancer Centre

When I started working in the clinic in the 1980s, the only treatment options we had for cancer patients were surgery, radiotherapy and chemotherapy. In many cases these treatments work, which is why we still use them today, but they are all relatively non-specific. What’s changed since then is, firstly, our understanding of the molecular details of cancer and, secondly, how we used this knowledge to develop more targeted treatments.

In the early 1990s, there was a big shift towards such treatments. And for the field I work in, lymphoma, this started with the development of the first effective antibody treatments, like rituximab. This drug targets the surface of certain blood cancer cells. And it was a real breakthrough, changing the outlook for patients with several types of lymphoma and greatly improving their chances of cure in many cases.

Now, with greater understanding of the immune system, we’ve moved on from targeting the cancer cells themselves to being able to selectively control the mechanisms of the immune system using so-called checkpoint inhibitor drugs. And over the years to come that will move forward as we combine different sorts of immune treatments to make more specific, more personal approaches to immunotherapy, drawing on our ability to define the ‘danger signals’ in cancer cells with ever greater precision.

Screening – Professor Nick Coleman, group leader at our Cambridge Centre

There are screening programmes for bowel, breast and cervical cancer in the UK. But some issues associated with screening are increasingly being recognised and need to be addressed.

For example, some people are being diagnosed and unnecessarily treated for tumours that wouldn’t have harmed them. At the same time it’s vital that screening tests shouldn’t miss those cancers that will cause harm, so it’s important to improve their accuracy so that the benefits far outweigh the risks.

Looking to the future, we’re entering a world of molecular testing. For example, future screening tests could pick up signs of cancer in the blood, such as circulating tumour DNA. As the technology improves, blood tests could be used rather than more invasive tests used for screening at the moment, these blood tests could detect certain cancers in people at high risk. But this kind of blood test will only make a difference if they identify cancers that would otherwise have become harmful and if we have good treatments for these early-stage cancers, so tests and treatments need to be developed in parallel to help save lives.

We are still a long way from using this approach in the clinic. But, ultimately, we are getting closer to more accurate and cost-effective tests than those available today.

Genomics – Professor Sir Mike Stratton, director of the Wellcome Trust Sanger Institute

Over the past 20 years cancer genomics has seen many environmental, lifestyle, and genetic factors that cause cancer confirmed. While some genes were known to be important in cancer, the first cancer genome was only sequenced in 2009 and since then the field has accelerated rapidly.

Because of our knowledge of which genes cause certain cancers, we have cancer prevention programmes, diagnostic tests and treatments. But there are still many unanswered questions. We need to investigate not only the genes but identify all lifestyle and environmental factors and learn how they combine to cause cancer.

Our recently-funded Cancer Research UK Grand Challenge will sequence the DNA of thousands of cancer samples from people in many different countries around the world. We aim to discover the causes of each of these cancers, information that’s vital before we can offer tailored treatments.

To make personalised medicine a reality huge numbers of genomes need to be sequenced. In the future, I predict there’ll be more laboratories with computers processing DNA data, rather than labs with microscopes. Cancer is no longer a disease hidden in the shadows – we will reveal its secrets.

Image by Pfree2014 via Wikimedia Commons under CC-BY-4.0

Surgery – Professor Arnie Purushotham, our senior clinical advisor

Surgery is moving towards a ‘less is more’ approach. Previously, doctors used to be more cautious, removing healthy tissue to reduce the risk of cancer cells being left behind.

But now surgeons are using more precise methods to leave as much normal tissue in place, reducing side effects and improving patients’ quality of life.

It’s about using targeted surgery that’s appropriate for the disease in front of you.

There’s been an explosion in research to help this, including using new imaging methods based on optical and molecular techniques. Doctors are also using the tools available in more innovative ways.

They can flip the traditional order of surgery, radiotherapy and chemotherapy to try to shrink a tumour before removing it.

Or they might test out new treatments while a patient is waiting for surgery so that the way a tumour responds can help in choosing drug treatment after the operation.

I’m well aware that my colleagues may think that my vision for the future is heresy, but I see a world where, in some cases, other forms of treatment may cure a patient and leave surgeons turning their hand to other things.

Gabi, Justine & Michael