Research News

Scientists identify potential drug target for BRCA-mutated tumours

Image: Crystal structure of EXD2 exonuclease domain in spacefill format. Image generated from PDB

A new study has uncovered a previously unknown role for the enzyme EXD2, identifying it as a potential drug target for cancer therapy.

Researchers showed that by protecting replication forks – the site of DNA replication – from potential genetic errors, EXD2 is able to help copy genetic material.

The discovery also suggests that by blocking EXD2 in cells that already lack fully-functioning BRCA1 and BRCA2 proteins – which are also involved in DNA repair – cancer cells are unable to survive.

Harnessing synthetic lethality

A team at The Institute of Cancer Research, London, believe BRCA tumours’ reliance on EXD2 to stay alive could be used to pave the way for a brand new, targeted approach to treating cancer.

Importantly, mutations in the BRCA1 or BRCA2 genes account for up to 80% of inherited cases of breast and ovarian cancer.

The study, published in Molecular Cell, and largely funded by the ICR – a charity and research institute – highlights an approach known as ‘synthetic lethality’, which focuses on exploiting two key genes that cancer cells need to survive. Where one of these two genes does not function properly due to a mutation, blocking the other with a drug has a synthetic lethal effect, causing the cancer cell to die.

Furthermore, researchers showed that in cells lacking both EXD2 and BRCA1 or BRCA2, replication forks malfunctioned – producing a catastrophic level of DNA damage, and cells were unable to survive as a consequence.

Urgent need to overcome resistance

Scientists at the ICR are now screening for small molecule inhibitors that will block the function of EXD2. They are also exploring whether the probable drug target would be able to support survival of other cancer types – such as pancreatic and prostate cancer, which also have BRCA1/2 gene mutations.

Treatment for tumours with BRCA mutations has shifted recently with the approval of PARP inhibitors like olaparib. However, while these drugs often lead to positive responses in cancer patients, tumours eventually evolve resistance so the treatment stops working.

As a consequence, there is an urgent need for more effective targeted treatments that are able to overcome cancer drug resistance. This is the focus of the ICR’s planned £75 million Centre for Cancer Drug Discovery, which will house an ambitious ‘Darwinian’ drug discovery programme.

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EXD2 protects against replication stress

The study also sheds light on the function of EXD2, suggesting that it plays a key role in protecting cells against DNA damage during genome duplication.

As the DNA double helix is unwound and opened in preparation for DNA replication, two Y-shaped structures – known as replication forks – are formed. This is the area where proteins are assembled to coordinate the replication process.

Replication stress occurs when DNA mistakes or unusual DNA structures are encountered during replication, which can result in stalled replication forks.

The new study has shown that EXD2 helps stabilise and restart stalled replication forks – like an engineer fixing and maintaining the machinery that helps make copies of DNA. In this way, EXD2 avoids the generation of DNA damage and maintains genome stability.

Researchers revealed that EXD2 achieves this by counteracting fork reversal – a process where replication forks reverse their course when they encounter DNA mistakes.

Fork reversal is a key protective mechanism aimed at preventing DNA breaks – however, too much of it can be problematic. By counteracting it, EXD2 avoids uncontrolled DNA degradation and manages to restart the forks.

Understanding replication stress pathways

Professor Wojciech Niedzwiedz, Team Leader of the Genome Instability and Cancer group at the ICR, said:

“Our research shows that tumours with mutations in the BRCA genes need EXD2 to survive. This is really exciting from a clinical perspective, as it means that pharmacological inhibition of EXD2’s function could be a new therapeutic strategy to develop more effective targeted drugs for cancer treatment.

“Mistakes during DNA replication are one of the major drivers of tumour formation. For this reason, understanding how cells maintain their genomes error-free is key to diagnosis and treatment of diseases like cancer.”

The research received additional support from Cancer Research UK.

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New evolution-busting drug overcomes resistance in aggressive breast cancers

A new type of drug that blocks one of cancer’s key evolutionary escape routes from chemotherapy could be used to treat aggressive breast cancers, a new study has shown.

Scientists at The Institute of Cancer Research, London, found that the drug could reinvigorate the response to chemotherapy in cancers that had become resistant, in both cells grown in the lab and in mice.

The drug is being developed in collaboration with the company Boston Pharmaceuticals following a licensing agreement and is currently in a phase I trial, after originally being discovered in the Cancer Research UK Therapeutics Unit at the ICR thanks to funding from partners including Cancer Research UK, the Cancer Research Technology (CRT) Pioneer Fund, Sixth Element Capital and Breast Cancer Now.

The drug, known as BOS172722, works by forcing cancer cells through cell division too quickly – leading to fatal errors in parcelling out DNA.

The first clinical trial of the new treatment is now under way in solid tumours including aggressive triple-negative breast cancers – and the researchers believe it might also be effective against other fast-growing cancers including ovarian cancer.

The new study is published in the journal Molecular Cancer Therapeutics and was funded by The Institute of Cancer Research (ICR) – a charity and research institute – as well as by Cancer Research UKBreast Cancer Now and Sixth Element Capital LLP.

BOS172722 is an example of one of the new evolution-busting therapies that will be the focus of the ICR’s planned £75 million Centre for Cancer Drug Discovery.

The centre is a £75m project – and we now have less than £14m to raise. To make our building a reality, we urgently need your philanthropic support.

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Drug blocks key player in cell division

The drug was discovered at the ICR in the Cancer Research UK Cancer Therapeutics Unit. It blocks a molecule called MPS1, which plays a central role in controlling cell division.

MPS1 is involved in organisation of chromosomes during cell division, ensuring they are distributed correctly between daughter cells and making sure that cell division doesn’t go ahead until they have been parcelled out evenly.

By blocking MPS1 using the new drugs, cancer cells speed through cell division with the wrong number of chromosomes and die as a consequence.

The ICR researchers found that cancer cells in dishes treated with the MPS1 inhibitor went through cell division in just 11 minutes, compared with 52 minutes without the drug.

And fast-dividing cells, from triple-negative breast cancers, ovarian and lung cancers, were especially sensitive to the effects of blocking MPS1.

Currently, people with triple-negative breast cancer receive taxane chemotherapies, such as paclitaxel, as their standard care.  Paclitaxel also affects the distribution of chromosomes during cell division but blocks the cell from dividing, which causes the cell to die. However, some cells escape becoming resistant to the drug and giving rise to more tumours.

Phase I trial under way

Treatment with paclitaxel in combination with BOS172722 dramatically reduced time in cell division – from 110 minutes with paclitaxel alone to 15 minutes when combined with BOS172722. All cells treated with the combination divided with gross chromosomal abnormalities and died as a result, whereas 40 per cent remained alive with paclitaxel alone.

The MPS1 inhibitor was also effective at lower doses when used in combination with paclitaxel in mice, and was well tolerated by mice at the doses that almost completely eliminated the tumours.

Professor Spiros Linardopoulos, Professor of Cancer Biology and Therapeutics at The Institute of Cancer Research, London, who led the study, said:

“We have discovered a brand new type of cancer treatment that uses cancer’s rapid growth against it, by forcing cells through cell division so quickly that they accumulate fatal errors. The drug works especially well in combination with chemotherapy in triple negative breast cancer cells – the deadliest form of breast cancer for which there are few successful treatments.

“Crucially, the combination is anticipated to be effective in cancer patients that have already become resistant to chemotherapy alone and has the potential to become a much-needed extra treatment option that could extend the lives of patients.

“The phase I trial of this combination is currently well under way and I look forward to the results.”

World’s first ‘Darwinian’ drug discovery programme

Professor Rajesh Chopra, Director of Cancer Therapeutics in the new Centre for Cancer Drug Discovery, said:

“Cancer’s ability to evolve and become drug resistant is the cause of the vast majority of deaths from the disease. We plan to counter that ability with the world’s first ‘Darwinian’ drug discovery programme within our Centre for Cancer Drug Discovery, dedicated to creating a new generation of anti-evolution treatments.

“Our new MPS1 inhibitor is a great example of a drug that seeks to outsmart cancer by blocking off a key evolutionary escape route, and in doing so we believe it can breathe new life into a chemotherapy that had ceased to be effective.”

Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, which helped to fund the study, said:

“It’s really promising that combining this newly-discovered drug with a standard chemotherapy could, in future, provide a new way to treat triple negative breast cancer and may even prevent the disease from becoming resistant to treatment.

“With triple negative breast cancer still lacking in targeted treatments, we urgently need to find new options to stop more women dying. This exciting study shows how well these drugs complement each other at a molecular level to destroy cancer cells.

“We now look forward to the results of clinical trials to understand whether this approach may be as effective and safe in humans. In the meantime, anyone with questions about their breast cancer treatment can call our free Helpline on 0808 800 6000 to speak to one of our expert nurses.”

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Personalised ‘liquid biopsy’ could detect return of breast cancer nearly eleven months earlier than hospital scans

A personalised blood test for women with early breast cancer could detect the return of the disease nearly eleven months earlier than hospital scans, a new study at five UK hospitals has found.

The study, funded by Breast Cancer Now and other collaborators, found that the test for levels of cancer DNA circulating in the blood detected the return of the disease after treatment on average 10.7 months before patients developed symptoms or secondary tumours became visible on scans.

The test, developed by scientists at The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust, was found to work in all types of breast cancer, and could detect the early signs of the spread of the disease around the body (outside of the brain).

Further research is now needed to understand how the test could be used in the clinic to help guide treatment and improve patient outcomes, with UK trials now underway to assess new treatments alongside the test in triple negative breast cancer.

Who is the test for?

Breast cancer is the UK’s most common cancer, with around 55,000 women and 350 men being diagnosed each year in the UK.

While more women are now surviving the disease than ever before thanks to research progress and advances in NHS treatment, recurrences are still common and happen when breast cancer cells survive initial treatment and grow into new tumours.

In cases where the disease returns and spreads to form tumours in other parts of the body, known as metastatic or secondary breast cancer, while it can be controlled for some time it unfortunately cannot be cured. Almost all of the around 11,500 women and 80 men that lose their lives to breast cancer each year in the UK will have seen their cancer spread.

‘Liquid biopsies’ ― blood tests that can detect cancer DNA in the bloodstream ― have emerged as an exciting new field in cancer research in recent years. The tests aim to monitor how a patient’s cancer is responding to treatment in real-time, detect emerging resistance to treatment and spot any recurrences at the earliest possible stage.

Analysing cancer DNA to predict recurrence

In a new prospective study of 101 women across five UK hospitals, scientists led by Professor Nicholas Turner in the Breast Cancer Now Research Centre at The Institute of Cancer Research (ICR) assessed the potential of a new personalised blood test to detect recurrence in patients diagnosed with early breast cancer who had no signs of secondary tumours.

The tests are tailored to the make-up of each woman’s tumour to enable the levels of cancer DNA in their bloodstream to be monitored.

By analysing cancer DNA from tumour samples collected before treatment, the researchers identified mutations that could distinguish cancer DNA from all other DNA in the blood and could be tracked over time. Overall, in the 101 patients, 165 different trackable mutations were found, with 78 participants having one trackable DNA mutation and 23 patients having multiple mutations.

Blood samples were collected from participants every three months during their first year after treatment, and then every six months for up to five years thereafter.

To assess the test’s ability to detect recurrence at a molecular level in different breast cancer sub-types, the researchers combined the data with a previous proof-of-principle study to establish a bigger cohort of 144 patients.

At follow-up of approximately three years, 29 of 144 patients had seen their breast cancer return. 23 of these 29 patients had cancer DNA detected in their blood prior to relapse, with the ‘liquid biopsies’ spotting the signs of recurrence on average 10.7 months before their clinical diagnosis.

‘A new treatment paradigm for breast cancer’

With the test accurately indicating the return of breast cancer across all major subtypes, the authors suggest that upcoming trials could lead to “a new treatment paradigm for breast cancer”, in which therapy could be offered at the first signs of relapse at a molecular level, rather than at a later stage once symptoms have appeared.

In addition, the researchers also conducted a sub-analysis of 80 patients who had blood samples taken at their diagnosis – with circulating cancer DNA being detected in 41 of these women. These patients were found to be 5.8 times more likely to experience a relapse during the first three years after treatment than those without detectable levels of cancer DNA prior to treatment – demonstrating that the test may also have prognostic potential in the future.

The study is published in JAMA Oncology and was largely funded by Breast Cancer Now, with additional support from The Royal Marsden Cancer Charity and the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the ICR.

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Professor Nicholas Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

“These new blood tests can work out which patients are at risk of relapse much more accurately than we have done before, identifying the earliest signs of relapse almost a year before the patient will clinically relapse.

“We hope that by identifying relapse much earlier we will be able to treat it much more effectively than we can do now, perhaps even prevent some people from relapsing. But we will now need clinical trials to assess whether we can use these blood tests to improve patient outcome. We have launched the first of these studies already, and hope to launch large studies in the future.”

‘Extremely exciting’ potential

Dr Simon Vincent, Director of Research at charity Breast Cancer Care and Breast Cancer Now, which funded the study, said:

“This could be a really significant breakthrough. The potential of this blood test to in future spot the signs of breast cancer returning or spreading much earlier in NHS clinics is extremely exciting.

“But we now need upcoming trials to identify whether offering treatments to patients at this stage could actually help intervene and improve their chances of survival or quality of life.

“The fact that these tests are personalised to each patient to try to find out whether any cancer cells remain and are on the move is unique. But for thousands of women, a blood test like this and the hope of new treatments to stop the disease returning just cannot come soon enough. The fear of breast cancer coming back can have a major impact on patients’ lives, and we urgently need to do more to support them, as well to increase awareness of the signs and symptoms of secondary breast cancer.

“While most aches, pains or coughs won’t mean the cancer is back, we’d encourage all women to report any new, unexplained or persistent changes to their GP or breast care team. Anyone feeling worried about their breast cancer returning can call our free Helpline on 0808 800 6000 and speak to one of our nurses.”

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Cancer trades in sugar for fatty acids in order to spread around the body


Scientists have uncovered a crucial change in cancer cells that allows them to spread around the body – by switching from sugar to fatty acids to fuel their growth.

Changing their ‘diet’ in this way allows tumour cells to set up shop at new sites where resources such as glucose – their preferred food source – are limited.

Researchers at The Institute of Cancer Research, London, found that a protein called AKR1B10 helps cells adapt the ways in which they get their energy.

When cancer cells have high levels of AKR1B10, it reduces their dependency on sugar and increases their ability to use fatty acids as a fuel source instead.

Shutting down cell food sources

The research raises the opportunity to screen breast cancer patients for increased levels of AKR1B10, which may help identify patients at an increased risk of metastatic relapse.

It could also lead to the development of new treatment options  that shut down cells’ ability to use fatty acids – which the study showed could reduce relapse rates in mice.

The study was published in Nature Communications and funded by Breast Cancer Now. The study focussed on breast cancer cells, but high levels of AKR1B10 are also seen in liver, lung, and pancreatic cancers.

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The researchers first identified AKR1B10 in a screen for proteins which, when expressed at high levels, helped cancer get ahead at new locations, while low levels of the protein hinder its growth in new organs.

Cells normally avoid using fatty acids for fuel as there are toxic side effects. High levels of AKR1B10 limit these toxic side effects, allowing cancer cells to thrive in new areas in the body.

The opposite is also true – switching off the cancer cells’ ability to use fatty acids reduces their ability to form tumours at new sites in the body.

Cancer survival mechanisms

Professor Clare IsackeProfessor of Molecular Cell Biology in the Breast Cancer Now Toby Robins Research Centre at the ICR, said:

“Cancer cells have to work hard to take root and form a tumour. When tumour cells head on the move to other parts of the body, a process called metastasis, they have to work even harder to adapt to the energy and nutrient sources available to them wherever they find themselves, as well as surviving the journey.

“Our study has shown the importance of cancer cell learning how to use different nutrients and energy sources in order to survive.

“We found that high levels of the protein AKR1B10 help tumour cells adjust to new environments as cancer spreads from the breast to other organs such as the lungs.

“This research significantly improves our understanding of cancer cell metabolism and metastatic relapse and could lead to new avenues of exploration for new therapies and treatments for patients with metastatic breast cancer.”

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Targeted breast cancer drug – olaparib – given green light by EU

European Medicines Agency approves olaparib for women with BRCA-mutant breast cancer – 15 months after licensing in the US

The targeted cancer drug olaparib has been approved by the European Medicines Agency (EMA) for women and men with advanced breast cancer who have inherited BRCA gene mutations.

The decision comes 15 months after the drug was approved for breast cancer in the US by the Food and Drug Administration.

NICE has paused its appraisal of olaparib for NHS patients with breast cancer while waiting for manufacturer AstraZeneca to submit new data, and is not now planning to restart its review until around July.

The Institute of Cancer Research, London, discovered the genetic targeting of olaparib – which became the first cancer drug directed against an inherited genetic fault when licensed by the EMA for BRCA-mutation ovarian cancer in December 2014.

In a statement, the ICR welcomed the approval of olaparib for breast cancer as an important step towards making it available for NHS patients – but also criticised delays in making the drug available in Europe.

‘Extremely innovative treatment’

Professor Paul Workman, Chief Executive of the ICR, said:

“It’s fantastic news that olaparib has finally been given the green light by the EMA for people with BRCA-mutant breast cancer. But it’s also been enormously frustrating for patients across Europe to have had to wait so long to get the drug.

“Olaparib is an extremely innovative treatment which was the first cancer drug in the world to target inherited genetic faults. Yet it’s taking far too long for pioneering drugs like this to reach patients and we need to do more to fast-track the most exciting new treatments into the NHS.

“The EMA and NICE have started to be more nimble and flexible in their evaluation of evidence, but there is still more they could do and much that they could learn from best practice in the US and elsewhere.”

Researchers at The Breast Cancer Now Toby Robins Research Centre lead important study programmes to understand the genetic and environmental causes of breast cancer.

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‘Excellent news for patients’

Professor Andrew Tutt, who is Director of the Breast Cancer Now Research Centre at the ICR, was part of the early laboratory research at the ICR behind PARP inhibitors in patients with BRCA mutations, and led some of the early clinical trials of olaparib for BRCA-mutant breast cancer.

Responding to the decision, Professor Tutt said:

“Although the delays have been disappointing, I am delighted olaparib has now been licensed in Europe for advanced breast cancer in women who have inherited BRCA1 or BRCA2 mutations. It is excellent news for patients with this form of breast cancer.

“Olaparib is the first drug to be approved that is directed against an inherited genetic mutation. It is a perfect example of how understanding a patient’s genetics and the biology of their tumour can be used to target its weaknesses and personalise treatment.”

Emma Clarke, 46 from Cheshire, was diagnosed with primary breast cancer in 2016, and secondary breast cancer spread to her bones in 2018. Later genetic testing discovered she carried a BRCA1 mutation. She is currently being treated with chemotherapy and is due to begin radiotherapy soon. Her daughter recently discovered she also has the BRCA1 mutation.

Emma said:

“I have done a lot of research into my type of cancer – about having a BRCA1 mutation and the possible treatments available for me. Because I have the BRCA1 mutation, and that carboplatin is working well for me at the moment, I found out that olaparib has a good chance or working well for me and that it is already available in the US.

“I’m fortunate enough to be a private patient and have asked my doctor about starting olaparib, which I will begin taking as a maintenance treatment when my radiotherapy finishes in June.

“I whole heartedly support progress in targeted therapies and getting these to patients as soon as possible. Targeted therapies are at the forefront of treatments for patients, and give such hope at extending lives while living with fewer side effects than traditional chemotherapies.

“I was really surprised to see the length of the time gap between olaparib being available in the US and it being approved by the EMA. I hope for all the other BRCA+ breast cancer patients in this country that it is available on the NHS as soon as possible.

“With advanced-staged cancers like my own, once you have good evidence that a new targeted treatment is shown to work and extend lives, it should be available to patients.”

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ASCO 2019: New blood test predicts breast cancer’s return at start of treatment

Video: Dr Ben O’Leary discusses a new blood test for women with advanced breast cancer which can predict
how well patients will respond to a new drug right at the start of treatment.

A new blood test for women with breast cancer can predict how well patients will respond to a new drug right at the start of treatment.

The new blood test detected genetic changes within women’s breast cancers which indicated that these patients were less likely to respond to treatment – and that their disease could be expected to come back quickly.

Targeted drugs have shown benefit for many women with advanced breast cancer, but some patients stop responding soon after starting treatment as their cancer evolves to become drug resistant.

In future, the new test could help identify nearly half of women with the most common form of breast cancer who are at the highest risk of early relapse – who will need further trials of new treatments to stop their cancer becoming resistant – as well as identifying those who will do very well on treatment.

Many scientists from The Institute of Cancer Research, London are attending the 2019 ASCO conference in Chicago. See all of our news, blog and video content from the event. 

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Early relapse

Scientists at The Institute of Cancer Research, London, analysed fragments of cancer DNA that have entered the bloodstream to study the effect of genetic changes in a woman’s tumour – often called liquid biopsies.

They took blood samples from 310 women with oestrogen receptor positive breast cancer – the most common form of the disease – who were taking part in a clinical trial of palbociclib and fulvestrant for advanced breast cancer.

The team found that 131 women – 42 per cent – had one or more of three changes in the tumour DNA circulating in the bloodstream that put them at risk of early relapse.

The research, presented today (Saturday) at the 2019 ASCO Annual Meeting in Chicago, was funded by the Medical Research CouncilBreast Cancer Now, and the manufacturer of palbociclib, Pfizer.

The p53 gene

Researchers at The Institute of Cancer Research (ICR) – a charity and research institute – and The Royal Marsden NHS Foundation Trust examined the impact of specific genetic changes within patients’ cancers at the start of treatment.

Women whose circulating tumour DNA contained changes in the well-known cancer gene, p53, saw their cancer come back after an average of 3.7 months, compared with 12.7 months in women without p53 gene changes.

An increase in the number of FGFR1 gene copies and a high level of tumour DNA in the bloodstream also shortened the average time before a woman’s cancer came back.

Women with these changes in circulating tumour DNA saw their cancer return after an average of 3.9 months compared with 12 months in women without these changes.

The study also found a link between faults in the p53 gene and the number and location of sites in the body to which cancer had spread.

Next, the blood test needs to be evaluated as part of different clinical trials to assess its value in other groups of patients, before it can start benefiting women with advanced breast cancer in the clinic.

The research follows a recent announcement by the ICR of a £15 million fundraising drive to complete a new £75 million Centre for Cancer Drug Discovery focusing on overcoming cancer evolution and drug resistance.

Predicting cancer’s next move

Professor Nicholas Turner, Professor of Molecular Oncology at The Institute of Cancer Research (ICR) and Consultant Medical Oncologist at The Royal Marsden, said:

“Exciting new targeted treatments like palbociclib are beginning to have a real impact on survival for women with breast cancer, but unfortunately many tumours which initially respond will later develop resistance and come back.

“Our study found that a new genetic test could detect right at the start of treatment those women whose cancers were most likely to develop resistance quickly to palbociclib. We could then adjust their treatment plan accordingly – trialling additional treatments from the outset to try and prevent resistance, or planning for a switch to another treatment as soon as resistance develops. We now need to assess in a clinical trial whether helping direct women’s care with this new test can offer improved survival and quality of life.”

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Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

“Cancer’s ability to evolve to become resistant to treatment is the greatest challenge we face in improving patients’ survival and quality of life.

“So-called liquid biopsy tests like this one are a key part of our toolkit in staying on top of cancers’ adaptability and evolution, and picking up the earliest signs of drug resistance. Detecting the potential of cancers to evolve resistance could allow us to predict cancer’s next move and to respond with adaptable new treatment plans.

“This study is a demonstration of the exciting new ‘Darwinian’ approach to treatment we will be taking once we have raised the money to complete our new £75 million Centre for Cancer Drug Discovery.”

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Capturing cancer on the move – ICR photography competition showcases stunning images of tumour cells in action

Every year our researchers submit outstanding pictures to our Science and Medical Imaging Competition – telling a story about our pioneering work and its benefits for patients. Check out the fantastic images selected by our judges, and this year voted for by the public.

Each year, The Institute of Cancer Research runs a Science and Medical Imaging Competition – designed to cater for the moments in the lab or the clinic where science meets art.

The entries we receive for the competition have all been created in the course of our pioneering cancer research – but they are also exceedingly beautiful, and wonderfully effective at conveying broad messages about our work.

‘Divide and conquer’

The winner of this year’s competition – ‘Divide and conquer’ by ICR postdoc Dr Maxine Lam – is a great example. It shows a replicating cancer cell in vivid detail as it invades through blood vessels – and communicates something about the lethal process of cancer metastasis that words alone often struggle to convey.

Metastasis is one of the most challenging aspects of cancer, because it often makes the difference between life and death. Once cancer has spread to other parts of the body we have few effective treatments, and the disease is often fatal.

Scientists are therefore keenly interested in understanding how cancer cells spread so they can find ways of stopping it from happen.

And that has led to the development of ever more sophisticated and powerful imaging technologies so researchers can watch the process in action over time.

“I’m really excited and honoured to have won”

Dr Lam’s winning image was taken using a technology called confocal microscopy, and shows a cancer cell in pink invading through a layer of blood vessel cells, in yellow and cyan. The cancer cell has created a gap in the layer of blood vessel cells as it invades.

The picture illustrates a key step in metastasis called extravasation – where cancer cells move out of a blood vessel into tissue to spread to secondary tumour sites. Despite the importance of this step, very few models exist in the lab to directly visualise and understand it.

Dr Lam’s lab in the ICR’s Division of Cancer Biology uses a unique set-up to provide previously unseen detail into this process.

In the image white DNA inside the cancer cell has condensed into bright rods. This means that the cancer cell is in the process of dividing itself, even as it is invading – a remarkable yet terrifying sight. Dr Lam’s lab is using images like this to identify factors that could prevent cancer cells from being able to move and spread.

Dr Lam said: “I’m really excited and honoured to have won the ICR Science and Medical Imaging competition. This image captures two important moments in the life of a cancer cell, when it divides to make new copies of itself and when it leaves the circulation and invades new tissues, which is one of the most dangerous aspects of cancer.

“Seeing this process in action helps us to better understand how cancer spreads, and I hope this will help with developing new treatments.”

The public’s favourite

Dr Lam’s image was awarded the main prize in the competition by a panel of judges from the ICR and our partner hospital The Royal Marsden NHS Foundation Trust.

We also this year carried out our first ever public vote, asking our supporters on social media to choose their favourite from the judge’s shortlist.

There was lots of agreement between the judges and the public, but the vote picked a different winner – a stunning time-lapse image of a breast cancer cell on the move by PhD student Patricia Pascual Vargas.

Patricia Pascual Vargas’ photograph: Time-lapse image of a breast cancer cell on the move

Cancer cells can take on many shapes, squeezing through tissues and finding their way into places they shouldn’t be, using a complex network of adhesion molecules on their surfaces to move around.

Patricia’s image was taken using another type of technology called a total internal reflection fluorescence microscope (TIRF), and shows a very aggressive type of triple-negative breast cancer cell sensing its environment, by making contact through structures called focal adhesions.

This time-lapsed image uses different colours to show the position of focal adhesions over time. The yellow and red colours represent shorter adhesion times, and show that the cell is moving down and to the left.

Patricia and her colleagues are looking at how targeting certain genes affects the formation of adhesions, changing the cell’s shape and how it moves. It could be possible to prevent cancer cells from spreading around the body, making cancer easier to treat.

Patricia said: “I’m thrilled to have won the first ever public vote. My image helps to demonstrate that cancer cells aren’t static – they move and change shape, and this important characteristic helps them to adapt to their environment. By pinpointing how cancer cells do this we could prevent them from changing shape and stop them from spreading, which could save patients’ lives.”

Our fantastic shortlist

With another year of so many astounding entries, it’s important to recognise all of the fantastic images that made it onto our shortlist.

Dr David Mansfield

Cell death caused by radiotherapy – before and after, taken by Dr David Mansfield, Division of Radiotherapy and Imaging.

David Mansfield’s photograph: Cells within a tumour visualised before (left) and after (right) radiotherapy

This image shows cells within a tumour visualised before (left) and after (right) radiotherapy. Coloured immune cells move in to clear up the tumour cells in white, left behind after treatment. This helps the body gain vital anti-tumour immunity and long-term protection from recurrent disease.

Multiple members of the Clinical Studies Division

Detecting immune cell populations in a liver biopsy by Dr Mateus Crespo Dr Bora Gurel, Ana Ferreira, Rita Pereira, and Professor Johann de Bono, Division of Clinical Studies.

Photograph by multiple members of the Clinical Studies Division: Detecting immune cell populations in a liver biopsy

This multi-coloured image was taken using multiplex immunohistochemistry to light up a liver biopsy from a patient with metastatic cholangiocarcinoma, an aggressive cancer of the bile duct. Liver cells in yellow are being infiltrated by immune system T-cells in red and green.

Parames Thavasu

The exploding nuclei – using combination drug treatments to overcome DNA damage repair mechanisms in cancer cells, by Parames Thavasu, Division of Cancer Therapeutics.

Parames Thavasu’s photograph: cells of an aggressive form of breast cancer called triple-negative breast cancer

This image shows cells of an aggressive form of breast cancer called triple-negative breast cancer, which is difficult to treat and has poor outcomes. After treating with a drug combination that causes damage to DNA at different stages of cell division, ‘explosive’ damage to cancer cells has occurred.

Dr Rebecca Marlow

Proliferating cells in a tumour organoid of triple-negative breast cancer, by Dr Rebecca Marlow, Division of Breast Cancer Research.

Dr Rebecca Marlow’s photograph: Proliferating cells in a tumour organoid of triple-negative breast cancer

This image shows tumour organoids of triple-negative breast cancer, a hard-to-treat form of the disease, grown from tissue samples donated by patients.

The nuclei of cells are marked in blue, while the cytoskeleton that helps cells maintain their shape is green. Proliferating cells are pink, where cells in the organoid are growing and dividing.

Cutting-edge research

These eye-catching images illustrate just some of the cutting-edge research being carried out at the ICR, taken using sophisticated equipment purchased thanks to generous donations from our supporters.

From images like these our researchers are gaining unprecedented insights into the mechanisms that drive cancer, and new ways to target the disease to help treat patients.

Dr Chris Bakal, who leads the teams in which Maxine and Patricia work, and is a previous winner of the competition himself, said:

“It is a cancer’s ability to spread round the body which often makes it fatal. It is incredibly valuable to be able to image this process over time to give us the insights into cancer biology that we need to discover new treatments.

“Our winners have used cutting-edge imaging technology to create measurable, single-cell imaging in 3D environments, to provide a vivid picture of exactly how cancer cells metastasise.”

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Potential new treatment for advanced cancers

A potential treatment for therapy-resistant breast cancer patients has been uncovered by researchers at Cardiff University.

The European Cancer Stem Cell Research Institute, based with Cardiff University, has repurposed a current cancer therapy, TRAIL, to find a new treatment for advanced cancers that are resistant to anti-hormone therapy.

Up to 75% of women diagnosed with breast cancer will have a cancer driven by oestrogen signalling and almost all of these women will receive anti-hormone therapy, like Tamoxifen or Aromatase inhibitors, to treat their cancer. Unfortunately, up to 40% of patients receiving these hormone therapies will develop a resistance to them, leading to relapse with aggressive cancer.

Dr Luke Piggott, European Cancer Stem Cell Research Institute at Cardiff University, said: “Part of our research focus is to develop new therapies, with low levels of side effects, for breast cancers that are resistant to anti-hormone treatments.

“TRAIL has already been tested in multiple types of cancer, but hasn’t yet proved beneficial to patients. But we believe we have demonstrated that patients who develop resistance to treatment will benefit from TRAIL therapy, as we have identified specific changes in the cancer cells from these patients, which mean that their tumours become sensitive to TRAIL treatment.

“Additionally, we have shown in this patient group that TRAIL treatment targets a specific type of cell in a tumour called a cancer stem cell. Cancer stem cells differ to the other cancer cells, as they are the cells responsible for initiating tumour growth and spread, and have also been shown to be resistant to therapy.”

Dr Richard Clarkson’s team of researchers at the European Cancer Stem Cell Research Institute tested TRAIL on tumour samples collected from cancer patients who had developed resistance to anti-hormone therapy.

Their findings showed that TRAIL selectively killed cancer stem cells from these patients but that tumours that had not developed resistance to tamoxifen were unaffected by TRAIL.

Dr Richard Clarkson said: “Cancer stem cells are the cells responsible for relapse and for the spread of cancer, so by targeting these cells, along with the bulk of the tumour, we could transform the way we treat cancer, especially for those that are resistant to anti-hormone treatments.”

82 percent of the anti-hormone resistant tumour samples showed a significant response to TRAIL, whereas only 8 percent of tumour samples that had not previously seen anti-hormone therapy responded.

The experimental models showed tumour shrinkage after being treated with TRAIL and there was also a reduction in the number and size of tumours that have spread to other organs, a process known as metastasis.

Dr Clarkson added: “Although we have more research to do before this new drug gets into clinic, TRAIL represents a very promising therapy for a population of patients where there is currently very few options.”

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