Research News

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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Our Recent Research News

We have recently provided funding to the Institute of Cancer Research (ICR) to help support their ground-breaking breast cancer research programme.

The ICR is one of the world’s most influential research organisations. They are the world leaders in identifying cancer genes, discovering cancer drugs and developing precision radiotherapy.

The ICR relies on support from charities, donors, partner organisations and the general public. It does not receive any government funding. That is why we chose the ICR as the first organisation to receive funding from us.

There are over 150 scientists and clinicians working at the ICR’s Division of Breast Cancer Research. The division focuses on identifying the genetic and environmental causes of breast cancer, so that they can improve diagnosis and treatment, and discover targets for cancer therapies.

Researchers at the ICR were responsible for one of the biggest discoveries in cancer genetics – the identification of the breast cancer gene BRCA2. This discovery has meant that people with a family history of breast cancer can be assessed for their future risk.

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Cell shape ‘maps’ could point to new cancer treatments

Scientists have created a ‘map’ linking the shape of breast cancer cells to the activation of their genes, which could point towards new treatments and help improve the effectiveness of immunotherapies.

In a revolutionary new approach, Cancer Research UK-funded scientists at The Institute of Cancer Research, London, used large sets of data to map out a network of links between cell shape and genes.

The researchers analysed cell shape in millions of images of more than 300,000 breast cancer cells, and data for more than 28,000 different genes.

Their study, published in Genome Research, found that changes in cell shape, which can be caused by physical pressures on the tumour, are then reflected in important changes in gene activity.

When they then used their maps to analyse thousands of samples taken from women who took part in the Cancer Research UK funded METABRIC study, the researchers discovered that these changes are linked to clinical outcomes for patients.

Hubs for information

They also identified key areas or ‘stations’ within the network that acted as hubs for the flow of information, controlling the levels of many other genes.

Specifically, they found that a protein called NF-kappaB plays a central role in this shape-gene network and could drive the growth and spread of cancer cells. This response was associated with tumour grade in patients and could be used to predict survival.

A map of the network of links between cell shape and genes

A map of the network of links between cell shape and genes (image: HebaSailem) 

These findings suggest that because NF-kappaB is rarely faulty in solid tumours, the surrounding mechanical forces are playing a large role in disease progression by switching the gene on. Because NF-kappaB is an important part of the immune response to cancer, this work also suggests immunotherapies might be improved by changing the mechanical forces in the tumour.

‘An exciting link’

Study leader Dr Chris Bakal, team leader in dynamic cell systems at the ICR, said: “Our study reveals an exciting link between the forces that act on cancer cells and the development of the disease.

“We used ‘big data’ approaches to carry out a complex analysis that would once have taken decades in a matter of months. The maps we’ve created of cell shapes and their effects on gene activity provide important pointers to new forms of cancer treatment, and ways of making existing immunotherapies more effective.”

Professor Karen Vousden, Cancer Research UK’s chief scientist, said: “Understanding the links between how a breast cancer looks and acts, alongside its genetic makeup, will help researchers develop a more detailed picture of the disease.

“The insights and approaches used in this research could one day lead to us being able to tell from appearance, how aggressive someone’s cancer is and how likely to spread, helping doctors decide the best course of treatment.”


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One thousand cancer patients have gene testing through efficient, affordable new process 16 NOV 2016

A thousand breast and ovarian cancer patients have now benefited from a faster BRCA gene testing process that was developed in the UK and is being adopted around the globe.

The 1,000th cancer patient has had ‘mainstream’ gene testing through an innovative process that offers affordable gene testing to cancer patients at their cancer clinic appointment.

The new approach was developed by researchers at The Institute of Cancer Research, London, through the Mainstreaming Cancer Genetics (MCG) programme, funded by Welcome.

Cancer patients could previously only access gene testing if referred to a genetics clinic. Referral criteria were complex and waiting lists for genetic appointments were long – many cancer patients did not get testing, even if they were eligible for it.

Patient-centred testing

The ICR and The Royal Marsden NHS Foundation Trust began an innovative pilot in 2013 to provide faster, more efficient and more patient-centred testing through routine cancer clinic appointments.

The pilot was quickly successful, and in 2014 mainstream gene testing of the BRCA1 and BRCA2 genes in eligible cancer patients became routine NHS care at The Royal Marsden.

In just the two years since, 1,000 cancer patients have had gene testing using the new process.

Professor Nazneen Rahman, Head of Cancer Genetics at the ICR and The Royal Marsden, said: “There were two main problems with the traditional system for gene testing. Firstly, gene itself testing was slow and expensive, and secondly the process for accessing gene testing was slow and complex.

“We used new DNA sequencing technology to make a fast, accurate, affordable cancer gene test, which is now used across the UK. We then simplified test eligibility and brought testing to patients in the cancer clinic, rather than making them have another appointment, often in another hospital.”

These two innovations have greatly increased the number of patients that can benefit from testing, without increasing costs.

Video courtesy of MCG Programme

Faster results

The Royal Marsden now offers tests to three times as many patients a year as it used to. The new pathway is also much faster, with test results received within four weeks compared with 20 weeks in the old system.

The gene test result helps patients to get the best management for their cancer.

Miss Fiona MacNeill, Consultant Surgeon at The Royal Marsden and President of the Association of Breast Surgery, said: “Having the BRCA test result is very helpful when discussing the surgical options with breast cancer patients. Some women with a BRCA mutation choose to have bilateral mastectomy because their risk of getting a new cancer in either breast is increased. It has been great to be able to quickly and directly arrange for testing at the cancer clinic.”

The results also provide information about whether hereditary causes of cancer are relevant for a patient’s family members. All women found to have a BRCA mutation have an appointment with the genetics team who coordinate providing information to relatives.

Many relatives choose to have a test to see if they have inherited the mutation. This allows them to make more informed choices and gives opportunities to reduce cancers in women found to be at high risk.

A cost-effective system

The patient response has been overwhelmingly positive with more than 95% of cancer patients wanting testing.

Professor Rahman added: “The main reason we wanted to change the system was because patients were telling us that they wanted to have better access to gene testing. We are delighted patients have found it so helpful and that it is more cost-effective for our cash-strapped NHS”.

“Many other centres across the country and internationally are adopting mainstream gene testing. This will help many women with cancer and will prevent cancers in their relatives.”

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