Worldwide Cancer Research Menu

Understanding a newly discovered way cells repair damage to DNA

Drugs that target the way cancer cells repair damage to their DNA have rapidly become successful at treating many different types of cancer. Simply put, too much DNA damage and the cell will die, so by blocking repair in cancer cells you can make them susceptible to DNA damaging agents such as chemotherapy.

Dr Ludovic Deriano and his team at Institut Pasteur, Paris, France, recently discovered two new genes, which play an important role in controlling DNA repair. They now want to discover exactly how these genes help to repair damage to DNA and reveal a novel molecular mechanism that could be used as a new therapeutic target for cancer.

Flicking the right switches to prevent cancer progression

One of the main issues facing cancer treatment is the patient’s development of resistance to drugs over time. To overcome this, many treatment regimens for cancer involve a combination of therapies and drugs.

Dr Cameron Bracken based at the University of South Australia, Adelaide, Australia is taking the first steps towards developing an entirely new combination therapy that aims to hold back progression of cancer. His teams focus is on small pieces of DNA-like material called micro-RNAs, which play an important role in switching off genes. The advantage of using these microRNAs is that they can each control many genes, which they hypothesise may make them a more potent block to cancer, and may make it less likely that cancers develop a resistance to therapy over time. They want to identify a combination of micro-RNAs that act in concert to stop the growth and spread of cancer, then use this as a therapeutic tool, delivering the micro-RNAs into cancer cells to prevent disease progression.

How a genetic parasite contributes to cancer development

Our DNA is a history book, telling the story of who we are and how we arrived here over hundreds of millions of years of evolution. Our genomes contain many ancient remnants of the past, including sections of genetic code known as “L1 retrotransposons” that have recently become of great interest to cancer researchers. These ancient bits of DNA are genetic parasites, hitching a ride on our DNA and able to “copy and paste” themselves throughout our genome.

L1 retrotransposons play a role in cancer but little is known about how they act to promote and maintain cancer. In over 50% of cases, the cancer genome contains more L1 retrotransposons then DNA from healthy cells, and the more the cancer genome contains, the more severe the disease seems to be.

The piece of genetic code contained within L1 retrotransposons carry the instructions that cells use to build two different proteins. And it’s only by interacting with other proteins in the cell that these proteins can make cancer cells grow and divide. Dr John LaCava and his team based at the Rockefeller University in New York, USA, are trying to unravel the network of interactions between these proteins to get a grasp of how L1 retrotransposons drive cancer. It is these discoveries that could open up new avenues for improving diagnosis and treatment of cancer.

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.

 

A new way to boost the immune system’s fight against cancer

Cells of the immune system that help fight off disease, including cancer, are switched on in special organs found in the body called lymph nodes. The immune system can also generate other areas to activate these cells, particularly where there is a region of diseased tissue, such as near a tumour. These special sites for switching on immune cells are called tertiary lymphoid structures, and it is known that for some cancers that the more of these structures that exist in or near a tumour, the longer the patient will survive.

Professor Maries van den Broek and her team want to work out exactly how these structures develop in the body to help develop a new cancer therapy that might be able to promote their development in patients. They are going to study in detail the impact these structures have on the immune response against tumours and importantly, how inducing the development of these structures might be able to enhance the effectiveness of standard cancer treatments.

Patching up tumour blood vessels

For a tumour to grow beyond a certain size it needs to be connected to the blood supply. Once this happens the cancer cells also have a route to escape and travel to other organs in the body. At this stage cancer is much more difficult to treat so it’s vital that we find ways to stop this from happening.

Dr Pipsa Saharinen and her team at the University of Helsinki recently discovered molecular mechanisms that cause blood vessels to become unstable. This ‘vessel leakiness’ is a stepping stone towards new blood vessels developing and is a crucial factor in tumours becoming connected to the blood supply.

Using funding from Worldwide Cancer Research, Dr Saharinen now wants to study in detail these molecular mechanisms, to find a weak spot that can be knocked out to prevent abnormal blood vessels. The hope is that this could ultimately lead to the development of new treatments that can prevent the spread of cancer.

Switching off DNA repair in cancer cells

Dr Maria Tresini is using funding from Worldwide Cancer Research to study an innovative way to switch DNA repair mechanisms off in cancer cells so that they can’t fix their damaged DNA causing them to die. Dr Tresini’s lab recently discovered a whole new molecular mechanism that cells have in their repertoire for DNA repair and now want to understand exactly how this mechanism works to see if can be exploited for cancer therapy.

The DNA in your cells is subjected all the time to damage that can lead to genetic mutations that cause cancer. In fact, research suggests that the DNA in each of your cells becomes damaged 20,000 times a day. It’s a good thing that our cells come equipped with multiple defence mechanisms that detect damaged DNA and repair it. But these repair mechanisms are also responsible for keeping cancer cells alive when they suffer DNA damage, including damage caused by chemotherapeutic drugs.

Dr Tresini is focusing on something called ‘R-loops’ - molecular structures that occur naturally when DNA becomes damaged. These R-loops are intriguing because they activate the DNA repair process in cells but at the same time make the DNA molecule unstable and more susceptible to damage. By understanding exactly how R-loops activate DNA repair it will be possible to identify ways to block the process with drugs. This could lead to a build-up of DNA damage in cancer cells that ultimately causes the cell to die.

Unpicking the role enzymes called sirtuins play in cancer

Dr Alejandro Vaquero and his team in Barcelona are trying to understand how a group of enzymes, known as Sirtuins, plays a role in the formation of tumours. They hope that by understanding more about these enzymes they will uncover ways to target them for cancer treatment.

Sirtuins are a set of enzymes that allow the cell to respond to environmental stressors such as hyperoxidative conditions, metabolic alterations or any DNA damaging conditions such as irradiation or damaging chemicals. These stress conditions are very relevant as they have been shown to contribute to tumour development. Sirtuins can influence the cell to respond in varied ways depending on the severity of the stress condition faced by the cell. Under certain circumstances Sirtuins will allow cells to adapt and survive but if the stress reaches dangerous levels Sirtuins can also instruct the cell to die. Due to these complex roles, alteration of some Sirtuins can help prevent tumours forming whereas others can actively help promote them. This complexity is in part due to the fact that some Sirtuins show two distinct enzymatic activities. Dr Vaquero wants to understand this enzymatic diversity and the specific contribution of each of these activities to the role of Sirtuins in cancer.

Drugs that block Sirtuins are already showing promise in clinical trials but because the enzymes have such a broad biological role there are many toxic side effects. Understanding more about these enzymes, including discovering new targets, could help identify better ways to target them and reduce side effects in patients.

Disrupting a cellular communication network

Dr Thomas Vaccari at the Department of Biosciences of the University of Milan in Italy, is using funding from Worldwide Cancer Research to identify weaknesses in a specific cellular communication network, called Notch signalling, which is implicated in a variety of cancers.

His team are using fruit flies to understand more about how this communication network functions. The gene Notch was discovered in the fruit fly but it turned out that the role it plays in normal development, growth, and even in the generation of tumours, is similar to the role it plays in humans. Dr Vaccari hopes that their research will reveal more information about the biological processes that Notch controls, which will ultimately lead to the discovery of a better understanding of its role in cancer.

Shutting off cancer’s energy supply

Dr Angel Nebreda and his team at the IRB in Barcelona are using funding from Worldwide Cancer Research to find out how cancer cells get their energy so that they can find ways to shut them down. Cancer cells are known to obtain their energy through different mechanisms to normal cells so understanding how they do it could reveal new ways to develop targeted treatments.

The team are particularly interested in a protein called p38-alpha MAPK, which they have begun to show plays a central role in the survival of cancer cells. They now want to study in greater detail exactly how this protein helps cancer cells to produce the energy they need to grow and divide and what happens to cancer cells if they try and block it off.