Worldwide Cancer Research Menu

Making radiotherapy more effective against cancers that have spread to the brain

Many cancers are now treatable thanks to improved diagnosis and effective treatments that target the primary cancer. However, as people live longer with cancer there has been a parallel increase in the number of people whose cancer returns – particularly in the brain. Brain cancer, and other cancers that have spread to the brain, can be very difficult to treat due to their location making surgery challenging, and the lack of drugs that can cross over into the brain and attack the tumour. Radiation therapy is a treatment option for tumours in the brain, but even though it has proven to be able to penetrate the brain, it doesn’t benefit every patient.

Dr Manuel Valiente and his team based at the National Cancer Research Centre, Madrid, Spain, have recently discovered that a specific protein found in cancers that have spread to the brain seems to be linked to the cancer being resistant to radiotherapy. Dr Valiente now wants to study this link in more detail to find out how this protein controls resistance to radiotherapy and its role in the spread of cancer to the brain. Ultimately, they want to work out if this protein can be used as a marker to identify patients that will benefit from radiotherapy, and see if they can target the protein therapeutically to make radiotherapy more effective.

Meet our Team Worldwide runners – it’s Laura Rawlings!

Running a marathon is no mean feat for anyone. Completing 26 gruelling miles is a huge achievement and we’re delighted to have such dedicated people who will be taking on the challenge this year at the London Marathon to raise money for Worldwide Cancer Research.

Completing a marathon to raise money for a good cause is a very selfless act but one of our Team Worldwide runners, 37-year-old Laura Rawlings from Devon, is doing it for herself as well as the countless others facing a cancer diagnosis. Laura has suffered from mental health problems and finds that running makes her feel a little better. It doesn’t cure her. It doesn’t fix all of her problems but it helps and she has chosen to turn that little piece of positivity into something great.

“I’ve been running on and off since 2014 and have always wanted to complete a marathon and couldn’t do it for a better cause,” she says. “I’ve struggled with mental health problems for years to the point where I’ve almost been sectioned and on bad days, I can’t leave the house. I’m unable to work because of it but when I run, it does help. It gives me a sense of freedom and time to myself to just think. It doesn’t fix things but it helps to lift my mood. This marathon will be a real personal challenge and I am determined to complete it.”

Like many others, Laura has family and friends who have suffered with cancer and chose to support Worldwide Cancer Research to help pioneering researchers to discover new, better ways to diagnose, prevent and treat cancer.

She is running in memory of her beloved aunt and to help support her good friend who is currently going through treatment.

“When I first started running, I ran for my Auntie Julie who had breast cancer at the time. We were like sisters and she was only 30 when she was diagnosed. Unfortunately she has since passed away. She had a double mastectomy but the cancer returned and it went into her bones. Nearly everyone in my family has been affected by some sort of cancer. One week after I found out I had a place in the marathon to run for Worldwide Cancer Research, I found out my good friend Hannah had breast cancer. I immediately cut my hair short to support her and my hair was past my bum so this was a huge deal for me. I donated the hair to help others going through cancer treatment.”

Laura starts her training in January. Although she’s not sticking to a rigid plan, she will be increasing the length of runs as she goes. “I’m not putting pressure on myself to make a certain time,” she says. “I’m just looking forward to turning up and doing it.”

As well as the run itself, Laura has been trying other novel ways to raise money.

“When we found out Hannah had breast cancer, my friends and I all wanted to help and so we staged a topless photoshoot to raise even more money and awareness, she says. “One of our friends is a boudoir photographer so it was very tastefully done. We want to generate as much awareness as we can and encourage women to check themselves. We had a real mix of women involved including a lady who has had reconstruction surgery. Local press were interested and we ran a competition to win a boudoir shoot and it was really successful. I’m just glad to do what I can to raise money and awareness for such an important cause and incredible charity.”

If you've been inspired by Laura's story and would love to join Team Worldwide, check out our list of amazing events which we have places for in 2019! And if you would like to donate in support of the fantastic work Worldwide Cancer Research funds, please click here.


Stopping tumours from hijacking the blood supply

Professor Robert Kerbel is using funding from Worldwide Cancer Research to work out how breast tumours that have spread to the lungs connect themselves to the blood supply. The team hopes this will lead to the development of an entirely new way of targeting the tumour’s vasculature to treat cancer that has spread.

Mouse models of cancer are currently the most common and initial way to test whether or not new treatments may be safe and effective to trial in patients. But we know that these models often can’t tell us exactly what will happen and so many drugs that show promise in such preclinical studies fail to work as effectively in patients once they enter advanced clinical trials.

One type of approved treatment that has partially fallen victim to this is a class of drugs called anti-angiogenics. These drugs are aimed at blocking the growth of new blood vessels from existing ones in a tumour (“tumour angiogenesis”) in the hope of cutting off the supply of oxygen nutrients that tumours need to keep growing and spreading. However, with some exceptions, these drugs have not worked as well in patients as originally anticipated, especially when treating metastatic disease that has spread to sites such as the lungs.

Professor Robert Kerbel and others have shown previously that this may be because secondary tumours connect to the blood supply in a different way to the primary tumour in that they can hijack the existing blood vessel supply. Now Professor Kerbel wants to understand how much this different process contributes to anti-angiogenic drugs not working optimally. He and his team also want to work out what the molecular features are of this process in the hope that it will help them identify whole new ways to target advanced cancers by selective targeted therapy of the hijacked blood vessels in tumours such as lung metastases.

Kick-starting the immune system in an aggressive type of breast cancer

The immune system is a powerful thing and findings ways to give it the kick it needs to become a weapon against cancer is a hotly pursued area of research. Professor Tony Tiganis at Monash University in Melbourne, Australia, is using funding from Worldwide Cancer Research to work out how to attract more cells of the immune system to breast tumours so that they can aid in eradicating cancer cells. His team are focused on the type of breast cancer called Triple Negative (TNBC) – the type that is most aggressive and can currently only be treated with chemotherapy.

Through their research they want to find out why some TNBCs have lots of immune cells known as tumour-associated lymphocytes (TILs) in the tumour, while others do not. The presence of more TILs within a tumour is thought to be associated with a better response to treatment and better overall outcomes for the patient. By unlocking this secret they want to be able to find new ways to help attract more TILs in TNBC to enhance the effect of treatment.

Novel drugs targeting the cells circadian rhythm offer new hope for future treatment of brain cancer

A study in mice shows how a new experimental drug could be a highly targeted treatment for brain cancer. The research, co-funded by the charity Worldwide Cancer Research and published in the journal Nature, establishes a path forward for generating a novel class of drugs that could also be used for a wide range of other cancers.

The researchers show that the drugs effectively starve the cancer cells to death by attacking their ability to sustain the high metabolic demand they need for continuous growth and replication.

The drug molecules, which are able to cross the protective barrier around the brain, reduced the growth of brain tumours, called glioblastomas, and lengthened survival time of mice. Results at this stage are similar to what is expected with the current standard of care for glioblastoma but with no toxicity or side effects.

In laboratory tests, the drugs also demonstrated selective cancer killing ability against breast, colon, leukaemia, brain and melanoma cancer cells with no apparent effects on normal cells. This data suggests that these drugs are a novel pharmacological tool for targeting cancer cells with high selectivity and low toxicity, against possibly a wide spectrum of tumours.

The researchers, led by Dr Satchindananda Panda at the Salk Institute for Biological Studies in La Jolla, California, found that the drugs work by interfering with the circadian rhythm (the internal “clock”) of cancer cells. The drugs activate a molecular component of the cellular clock, called REV-ERBs, which causes the cells to die.

Dr Panda, an associate professor in the Salk Institute’s Regulatory Biology Laboratory and senior author of the new paper, said: “We’ve always thought about ways to stop cancer cells from dividing. But once they divide, they also have to grow before they can divide again, and to grow they need all these raw materials that are normally in short supply.”

“Targeting REV-ERBs seemed to work in all the types of cancer we tried. That makes sense because irrespective of where or how a cancer started, all cancer cells need more nutrients and more recycled materials to build new cells.”

The researchers found that cancer cell death was induced because activating REV-ERBs led to the cells being unable to cope with the high metabolic demand created by their constant drive to grow and divide. They also found that the drugs could kill pre-malignant cells – or cells which are not yet proliferating uncontrollably but act as the seed to kick-start tumour growth – suggesting that treatment could be effective at eradicating those hard-to-treat, dormant cancer cells.

Dr Helen Rippon, Chief Executive of Worldwide Cancer Research, said: “Cancer cells often seem to have a broken internal ‘clock’. Not only does this disrupt the cells’ daily rhythms, but can also turn on molecular circuits that drive tumour growth.”

“Understanding these underlying faults at the root of cancer is essential if we are to develop completely new treatments that are more effective and have fewer side effects.  We are delighted that this research is already leading towards new treatments for brain tumours and that early results suggest it could be a fruitful approach for other cancers too.”

Stopping breast cancer spread

Despite the remarkable advances towards understanding breast cancer, most breast cancer related deaths are due to the onset of distant metastases (the spreading of cancer cells to form secondary tumours around the body) and a poor response to current therapies. One subtype of breast cancer, called triple negative breast cancer, has a particularly high frequency of spreading and poor response to standard therapies. This subtype represents ~15% of all breast cancers, and has the worst outcome, making the development of new treatment strategies is a priority.

Professor Morag Park explains “We have identified an alteration found in 60% of this subtype of breast cancer that contributes to cancer spread. This project aims to understand the mechanism through which this change, involving loss of function of a gene called Kibra, causes the disease to spread. We have developed mouse models that accurately mimic human breast cancer that lack the Kibra gene. We will identify how Kibra acts to stop breast cancer spread and how its loss enhances tumour cell invasion into neighbouring tissues. Our ultimate goal is to develop new therapeutic strategies to treat patients with triple negative breast cancer.”

Understanding exactly how invasive breast cancer cells break free

Dr Chavrier is working to understand how invasive breast cancer spreads around the body.

Breast cancer which has developed the ability to spread away from the original tumour is much more difficult to treat, and outlook for the patient is worse. But before they can develop new treatments targeting invasive breast cancer, scientists need to understand how breast cancer cells break away in the first place.

Dr Chavrier and his team already know that a specific cell protein on the surface of invasive breast cancer cells can perforate surrounding cell layers and form ‘tunnels’- helping the cancer cell escape away to other parts of the body. And they recently found that it is the nucleus- the cell command centre- which gives the order for the protein to act.

In this project the researchers will now investigate exactly how and why the nucleus makes this command, and what other proteins are involved in helping invasive breast cancer cells break free.

“We believe that this work will help inform development of future breast cancer treatments, and will ultimately help breast cancer patients” says Dr Chavrier.

How can short strings of nucleic acid lead to breast cancer drug resistance?

Breast cancer is the most common cancer worldwide and it claims more than half a million lives each year. Among the greatest challenges in its treatment is the resistance of some tumours or to chemotherapy. This often happens because the cancer increases the abundance of molecules that can inactivate the drug or expel it from the cell.

Dr Anna Git is studying RNA, a temporary copy of a small section of DNA, usually encoding instructions to make proteins. She told us "Some short RNAs, such as Vault RNAs (vtRNAs) do not code for protein, but are instead functional themselves. Of the four vtRNA types in the human genome, one can directly halt the growth of cancer cells. Two other types can attach to and seclude certain chemotherapeutic drugs, thus preventing their activity. Encouraging results have shown showed that altering the amount of vtRNAs in some lab-grown cancer cells substantially altered the cells' response to chemotherapy.

She explained "With my grant I propose to test how vtRNAs attach to a broad selection of drugs. I will also alter vtRNA levels inside cells to affect drug resistance in models of different types of breast cancer. Finally, I will identify proteins that recognise vtRNAs to understand how vtRNAs lead to drug resistance. In the future, I hope to help predict this mode of drug resistance in patients and perhaps avoid it altogether."

Why this research is important:

Chemotherapy remains our best weapon against many aggressive or advanced cancers. Unfortunately, the side effects of chemotherapy lay a heavy physiological, psychological and social burden on the patients and their families. If the tumour is resistant to the treatment, this burden is suffered in vain. While medical science has come a long way in understanding how chemotherapy works, we know far less about why it sometimes doesn’t. I hope that if I help understand which tumours are resistant to which chemotherapy I can help improve many patients’ quality of life by avoiding futile toxicity and allowing the earlier application of alternative treatments.

How does obesity increase the risk of cancer spread?

Being very overweight is linked to an increased risk of developing cancer, but researchers don’t yet know exactly why this is. Dr Hector Peinado Selgas and his team in Madrid have an idea, and they are using their Worldwide Cancer Research funding to investigate.

“Obesity is fast becoming a major problem for humankind.” Says Dr Peinado Selgas. “An obese person is more likely to develop cancers such as bowel cancer, breast cancer, and ovarian cancer. We want to map the biological processes which link obesity to cancer progression and cancer spread.”

“We already have data which hint that tumour cells and fat cells send small ‘parcels’, known as exosomes, to communicate with each other. In this new project we want to study how this exosome-based cross-talk could increase the risk of the cancer spreading.”

Dr Peinado Selgas and his team will use patient samples to investigate how the chemical make-up of the exosome parcels change depending on patient obesity and how their cancer progresses. “We can detect traces of these exosomes in the blood,” says Dr Peinado Selgas, “so ultimately we want to see if we can define specific exosome ‘signatures’ that might give a clue to how and when a person’s cancer might spread. This will also help us design new therapies to target the pathways which regulate cancer growth and spread.”

New year, new research

We support research into all cancer types and this latest grant round was no exception. The projects contain a good mix of cancer types from mouth and lip to breast, lung, pancreatic, lymphoma and liver cancer to name but a few. And of course a large amount is being spent on understanding the very fundamental principles behind how our cells behave and what goes wrong in cancer. Keeping with our ethos of supporting the best research around the globe, the projects are taking place all over the world including England, Portugal, Greece, Spain, Australia, The Netherlands, France, Germany, USA and Canada.

Opening up about mouth cancer

Some of the projects that most excite us are Dr Guy Lyons from the University of Sydney, Australia. He is identifying genetic changes that occur when mouth cancer starts so that it can be diagnosed early, when treatment is more likely to be successful. You can read more about mouth cancer in our recent blog. Dr Lyons told us “The support of organisations such as Worldwide Cancer Research for research into the fundamental biology of cancer is essential for the discovery of new paradigms that enable new approaches in the clinic down the track.”

Developing new ‘super cameras’

Professor Carolyn Moores at Birkbeck University of London in England is developing state of the art electron microscopy to actually visualise where drugs bind (stick) to their target molecules inside the cancer cells. This is VERY cool.  She said “Revolutionary new imaging technology means that our pictures will provide unprecedented detail, from which we will calculate the three-dimensional shape of our samples. This technique could potentially revolutionise the way drug discovery is carried out and our findings could be used to design specific drugs that can be further developed to improve treatments for cancers in the future. It is an exciting time to be an electron microscopist and we are thrilled that Worldwide Cancer Research is supporting our research in this area.”

Studying ‘bubbles’ to beating childhood brain cancer

We are also funding Dr Kasper Rouschop at Maastricht University in The Netherlands (pictured above) who is studying how ‘bubbles’ released by glioblastoma tumours encourage blood vessels to grow into the tumour. Glioblastoma’s are a type of brain tumour that commonly effects.  He told us “We anticipate that the results of this research will enable us to evaluate whether targeting these particular bubbles could be a potential new way to reduce the growth of brain tumours.  Our approach is highly innovative and is based on our previous identification of “bubbles” that are specifically released by hypoxic tumour cells. Without the support of Worldwide Cancer Research, evaluation of this promising approach would not be possible.”

And last, but by no means marking the end of my list of fab new projects, is Dr Ruben van Boxtel at the Hubrecht Institute in the Netherlands. He is trying to figure out why cancer arises in some parts of the body more than others. Great question to try to answer!

Our next grant round is already underway and our Scientific Committee will meet in March to decide who gets funded.  But this relies on donations, no money means no research.  If you would like to join team Worldwide Cancer Research and make a donation today just text WORLDWIDE to 70004 to donate £10. Thank you.

Image kindly provided by Dr Kasper Rouchop.