Joining the dots – how lab research can lead to new approaches for treating cancer

Professor Steve Jackson

Professor Steve Jackson’s research will help to improve cancer treatments in the future

At its heart, cancer is a disease that starts when genes go wrong. This can happen when the DNA in your cells gets damaged, for example by tobacco smoke, UV radiation in sunlight, or just the normal chemical reactions of life within our cells.

And, in some rare cases, specific inherited gene faults can also add to the mix.

To try to prevent cancer developing, our cells have evolved sophisticated ways to prevent this damage – collectively called the DNA repair system.

A number of cancer treatments, such as radiotherapy and some chemotherapy, also aim to damage cancer cells’ DNA, but so badly that they die. This leads to a problem – cancer cells can switch on their DNA repair systems to protect themselves against the damage, making these treatments much less effective.

So understanding exactly how cells repair their damaged DNA, both in health and in cancer, is vital for figuring out how this disease starts, as well as finding more effective ways to treat it.

Cancer Research UK’s scientists have a long and distinguished track record in understanding DNA repair. One of the world leaders in this field is Professor Steve Jackson at the Gurdon Institute in Cambridge, whose work we’ve funded for more than a decade. Together with postdoctoral researcher Abderrahmane Kaidi, he’s now managed to join the dots between three previously separate areas of research related to DNA repair

Their discovery, published in the prestigious journal Nature, sheds light on the fundamental mechanisms that detect and repair genetic damage, and points towards important new approaches for treatment.

Let’s look at their work in more detail.

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Innovative drug development fund backs first major project

Molecular machinery of a dividing cell. Image courtesy of Wikimedia Commons

MPS1 inhibitors block a molecule involved in cell division.

Last year we were extremely excited to launch an innovative fund to bring new cancer drugs to patients.

Today we’re pleased to reveal that the fund has given the green light to its first project, aimed at accelerating the development of a promising group of compounds called MPS1 inhibitors into effective new cancer drugs.

The £50 million fund has been developed to address the sobering reality that the process of turning promising investigational drugs into ‘real life’ treatments for cancer patients is very often unsuccessful. The fund, half of which is provided through our commercial company Cancer Research Technology (CRT), is central to our strategy to make sure that exciting drug discoveries don’t languish at the lab bench, but are given every chance to be transformed into future cancer cures.

Called the CRT Pioneer Fund, it’s being run by independent management firm Sixth Element Capital, who have spent the last few months selecting exciting drug discovery opportunities from around the country.

Read on to find out why work on MPS1 inhibitors by researchers at The Institute of Cancer Research, London, piqued their interest and led to the first grant from the Pioneer Fund.

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Expert Opinion – The challenges of lung cancer

Professor Dean Fennell

Professor Dean Fennell

One of our leading experts in lung cancer, Professor Dean Fennell, shares his thoughts on this devastating disease.

Lung cancer is an enormous health burden both in the UK and globally. It’s incredibly common and kills roughly 35,000 people every year in the UK alone – and more than 1.3 million people worldwide.

But despite its prevalence, and the strain it places on healthcare, progress in treating lung cancer has been slow.

Historically, the disease has always been viewed as one that’s difficult to treat, and this has led to a general lack of interest in trying to move treatments forwards. The reluctance to carry out research into lung cancer was further increased by the perception that we’d hit a plateau with treatment about 10 years ago, and many people in the field felt that we’d reached the limit of what we could achieve in this disease.

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Blood test tracks breast cancer

Blood test

A blood test could provide a simple way to monitor cancer

Cancer is a wily enemy. It mutates and spreads within the body and becomes resistant to treatment. Understanding and counteracting this tricksy behaviour is the greatest challenge for researchers and doctors, and is the key to bringing forward lasting cancer cures.

Thanks to advances in technology, we’re now starting to map out cancer’s underlying genetic landscape. In theory, if doctors knew exactly which gene faults were driving a patient’s cancer, they could give them the most appropriate targeted treatment.  

And as well as selecting the therapy with the best chances of working, it’s also important to know whether the disease is responding to treatment or not as fast as possible, so doctors can decide on the best course of action – for example, whether to continue with a particular drug or switch to a different one.

But there’s a problem with this approach. Monitoring how well a patient’s cancer is responding is not a simple job. At a minimum, it requires regular scans or other tests.  On top of this, analysing a tumour’s genes requires having a sample of it, usually taken as a biopsy with surgery, as well as access to tests that can provide meaningful results in a short timeframe. And if the cancer has spread to a multitude of locations in the body, it’s simply not possible to biopsy them all.

As an extra kicker, we now know that a single tumour can house cancer cells with a range of different gene faults – a characteristic that scientists refer to as “intra-tumoural heterogeneity”, but could also be described in rather more unpublishable words. And secondary cancers that have sprung up elsewhere in the body also have differences in their genetic makeup compared to the initial tumour.

The problems seem almost insurmountable – it’s a bit like trying to attack a shape-shifting army that we can’t properly see. But, as you might hope, research is coming to the rescue.

Building on work we talked about last year, scientists at our Cambridge Institute have made a significant step forward in developing a relatively simple genetic blood test that can monitor breast cancer as it progresses.

They’ve published their results in a paper in the New England Journal of Medicine, and although the title – “Analysis of circulating tumor DNA to monitor metastatic breast cancer” – may not set your heart racing, the contents are certainly inspiring for all of us hoping for progress in cancer research.
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Clinical trials: Helping more children beat cancer every year

A child on a clinical trial

Clinical trials have helped to save thousands of children’s lives.

December is childhood cancer awareness month, so we thought we’d focus on an area that contributed more to saving children’s lives from cancer than anything else – clinical trials.

More and more children are now surviving cancer, and today there’s over 33,000 long-term survivors of childhood cancer alive in the UK. Clinical trials are at the heart of this progress, testing new treatments or different ways of giving drugs to see if they’re more effective than what’s already available.

In the 1970s, when clinical trials for childhood cancers first started, fewer than three in 10 children with cancer survived. Today nearly eight out of 10 make it.

This life-saving progress is fantastic, but we can’t rest on our laurels. With more than 200 children losing their lives to cancer every year in the UK, we’re still searching for cures. And for those we can cure, the drugs they’re given need to be made kinder and with fewer side effects. This will give them the chance to live full, long lives without a lasting legacy from their treatment.

To help bring hope for the future we’re running clinical trials for children with cancer across the whole of the UK. Here are a few we’ve recently launched.

Finding better treatments for neuroblastoma 

Each year around 100 children in the UK are diagnosed with neuroblastoma, and many have access to immunotherapy through a Cancer Research UK trial opened three years ago. This new trial is offering immunotherapy to children and young people whose cancer has come back– around half of all cases. Doctors hope that this new trial will mean almost all children in the UK have access to this cutting-edge treatment.

The treatment works by ‘flagging up’ cancer cells to the immune system, so it can hunt them down and destroy them. As well as offering more children access to immunotherapy, the trial will also look at a different way of giving it. Immunotherapy has to be given with a strong pain killer such as morphine because it causes severe pain, meaning patients need to stay in hospital. This trial will see if giving immunotherapy more slowly and over a longer time reduces the pain it causes so children could stay at home while having it.

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Expert opinion: Professor Dion Morton – combining chemo and surgery in colon cancer

Earlier this month we announced trial results showing that giving patients with colon cancer (bowel cancer that originates in the colon) a short course of chemotherapy before surgery, could significantly shrink their tumour. This makes the tumour easier and safer to remove, potentially reducing the chances of it coming back.

We caught up with trial leader Professor Dion Morton, a surgeon based at the University of Birmingham, to find out when patients might begin to benefit from this potentially exciting advance.

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Headlines about ‘backfiring’ chemotherapy are misleading

An image of chemotherapy drugs

Some of today’s headlines about chemotherapy missed the point

We spotted some worrying headlines today claiming that chemotherapy can ‘backfire’ and ‘encourage cancer’, making it “tougher to tackle”. We want to make it clear that cancer patients don’t need to be distressed by these unnecessarily alarming headlines, or consider stopping their treatment.

In fact, the research from US scientists that sparked the coverage categorically does not show chemotherapy makes cancer harder to beat. Instead, the work gives scientists a vital insight into one way that the body can develop resistance to chemotherapy, and it could help explain why treatment sometimes stops working.

But it doesn’t tell us anything new about current chemotherapy treatments – we already know that some cancers respond to chemo while other don’t, or start growing again after treatment.

So it won’t change how doctors treat cancer patients today.

Read our own news piece about the research for the main facts, and read on for more detailed analysis of the research.

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