Behind-the-scenes at Cancer Research UK

We can send a man to the moon, so why can’t we beat cancer?

Just a few years ago, we at last reached the point where half of all people diagnosed with cancer could expect to survive it. Within 20 years, scientists hope that figure will rise even further to 3 in 4 people.

Reaching these milestones does not happen easily. It is the culmination of years of research by thousands of scientists around the world, working in fields as diverse as genetics, pharmacology and biochemistry – as well as medicine.

Much of this research takes place here in Manchester. In fact, cancer is one of The University of Manchester’s five main ‘research beacons’ – priority research areas in which we are world leaders – the others being industrial biotechnology, advanced materials, energy and addressing global inequalities.

Beyond the main university campus, we also have the Cancer Research UK Manchester Institute, situated over the road from the Christie Hospital in Withington, south Manchester. Their brand new £28.5 million building opened its doors last year, and is jointly funded by The University of Manchester, The Christie NHS Foundation Trust and Cancer Research UK.

Cancer Research UK is the world’s largest independent cancer research charity, and funds and conducts research into the prevention, diagnosis and treatment of the disease. Its work is almost entirely funded by donations from the public.

The Christie Hospital is one of Europe’s leading centres for cancer treatment and research, treating over 40,000 patients a year, and around 400 early phase clinical trials are taking place here at any one time. This makes The Christie an ideal next-door-neighbour for the new Cancer Research UK Institute.

Research in places like Manchester has vastly improved our knowledge of cancer and how we can treat it over the past decades. The discovery of epigenetics has shone a new light on the different ways this disease can arise, while genome sequencing has given us new and highly effective methods of diagnosis, allowing us to accurately tailor treatments to each individual’s needs.

There’s still such a long way to go however.

Cancer is not one disease nor one hundred diseases but many thousands, each unique and requiring a different response. Such a diverse assortment of diseases is only possible because the body itself is so diverse.

37 trillion cells, and 10,000,000 components per cell make the body 125 billion times more complicated than the Saturn Rockets that allowed humans to go to the Moon. It is only when we consider this staggering complexity that we can begin to appreciate the immense challenge we face in trying to treat the numerous different types of cancer.

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© NASA

 

 

HIV Treatment could be used to help treat skin cancers

Faculty scientists have made an important discovery in skin cancer treatments. They found that the HIV drug Nelfinavir can help treatments of melanoma to become more potent.

Skin cancer is a major problem in the UK, with more than 13,000 people being diagnosed with melanomas every year and over 2,000 people dying from it. There are drugs that are available to help treat melanoma skin cancer, but these can be ineffective because melanoma cells become resistant to them over time. After the resistance, the cells go on to make genetic changes which make it extremely hard to attack them.

Professor Claudia Wellbrock and her team found that Nelfinavir can help prevent cancer cells from becoming resistant to the treatment, making the cancer fighting agents more effective for a longer time.

The team discovered that cancer cells were able to rewire themselves by using a molecular change. This change that typically takes place in the first two weeks of cancer treatments, helps the cancer cells to develop resistance.

It was this molecular change that Wellbrock targeted by the use of Nelfinavir. It was found that Nelfinavir actually blocks the cells from rewiring and they were therefore less likely to develop resistance to the cancer treatment.

It is now thought that Nelfinavir could be administrated alongside existing cancer drugs in order to improve their effectiveness and boost the patient’s chances of survival.

Professor Wellbrock says:

“In the first few weeks of standard treatment for skin cancer, the cancer cells become stronger and more robust against treatment. But if we can target skin cancer cells before they become fully resistant, we would have a much better chance of blocking their escape. We think this research has brought us one step closer to making this a reality.”


The paper can be found at Cancer Cell   http://www.cell.com/cancer-cell/fulltext/S1535-6108(16)30037-X

 

Tuesday Feature episode 32: Liz Toon

Please explain your research for the general public.

I do a whole bunch of different kinds of research, with most of it focused around issues of women’s health and relationships between patients and doctors. One of the projects that I’ve been working on for a while is a history of breast cancer treatment and experience in 20th century Britain. What I want to know is how has treatment changed in Britain over the course of the last century, but also how has the experience of being treated for breast cancer changed.

In relation to my research, I am working on a newer project on women’s cancer screening and prevention.  Basically the project is about how interventions like cervical smears and the mammograms became expected parts of women’s healthcare. I am looking at how interventions become a way for women to think about the status of their health in their everyday lives; part of this looks at how these types of treatments were built into the National Health Service.

How does this research benefit the general public?

Breast cancer services in the UK are often used as a proxy for the state of Britain’s commitment to women’s healthcare and I want to know how this came to be. The project will also explain why certain practices are organised the way that they are, for example, you get cervical cancer screenings from your GP whereas you get breast cancer screenings through specialised centres and so my research hopes to answer how this happened. I think we all need to know why our healthcare system is set up this way.

The project also allows me to understand how everyday people receive health care; it gives me the ability to understand what it is like for patients who have to go through the current health care system in comparison to patients from earlier in the 20thcentury and how these changes in practices affect the patient.

How did you first get interested in the history of science and medicine?

Well it’s sort of a long path. I started out, like many people in the History of Science, Technology and Medicine, really interested in science as a kid. I used to like to read old medical books and old science books. I actually went to University in the US and I wanted to become a research biologist. I loved working in the lab but I was not so good at other elements of research and at the same time I found that what I really cared about was the history of science and medicine. Doing History is great for the curious, because it’s basically reading other people’s mail!

I worked for a while as a technical writer and then I went onto graduate school in history and sociology of science. At that point I decided I actually wanted to look at how it is that everyday people learn about science and medicine.

Did you have any science heroes growing up? Who inspired you?

I was a big reader as a kid and I loved reading biographies of scientists and I especially loved reading biographies of women scientists; Marie Curie of course, but lots of others too. Like a lot of people of my age group and that are American, the thing that really did it for me was Carl Sagan and Cosmos. I realised later that this was partly because he didn’t really just tell you the scientific information, but he gave you a really good picture of how that information came to be. He made it clear that you have to understand the history to really understand the present and the future and I think he was terrific at that!

How has working here in Manchester helped you?

It’s helped me a lot to work here in Manchester, especially at the Centre for History of Science, Technology and Medicine, because CHSTM is internationally known with a really strong sense of cross-discipline collaborations. I have great colleagues and there are a lot of elective and joint projects that we have going on and it’s really good in that sense because as a historian a lot of the work that you do is individual. When you sit in the archives you’re looking at papers on your own but being able to do historical projects whilst working with other people is really special. Manchester has been great!

Manchester has also been really great because there’s a lot of interest all over the University in the human elements of medicine. I have colleagues in Humanities, in Medicine and Human Sciences, and here in Life Sciences, that are not historians, who all want to think about the more human experience side of biomedicine. In fact, we’ve started a new group that’s called the Medical Humanities laboratory and that is bringing together those people from all over the University to look at the relationships between art, history and science.

What do you do outside of work?

Anyone who follows my Twitter Feed will know that I am a very avid knitter and crafter. I probably tweet as much about knitting as I do about history!

Anyone who has come to a CHSTM seminar will have probably seen me knitting during the seminar itself because it really does help me concentrate better. It allows me to get my nervous energy out by knitting a sock whilst I try to think of a question to ask. I also read a lot of mystery novels and, of course, I do a lot of things like travelling and visiting museums.

Faculty researcher receives grant for pancreatic cancer project

Dr Jason BruceFaculty researcher Dr Jason Bruce has been awarded a grant of around £180,000 by The Pancreatic Cancer Research Fund (PCRF.)

PCRF have awarded a total of £1.2million to ambitious projects tackling the UK’s deadliest cancer. It is the second year that they have invested over £1million in a single funding round, enabling innovative research that could lead to new treatments for this aggressive and complex disease.

Dr Bruce’s work focuses on pancreatic cancer cells and the unique way that they extract energy from the nutrients which help them to survive and grow. The cancer cells use this energy source to pump calcium out of the cell. As high levels of calcium can be fatal to such cells, Dr Bruce’s project will aim to utilise new drugs and cut off the supply of energy to the calcium pumps. This would kill cancer cells whilst leaving healthy ones unharmed.  Maggie Blanks, PCRF’s founder and CEO, said:

“This is an amazing achievement, and it is thanks to the tireless fundraising of our supporters around the country who know that funding research is the only way to accelerate the development of new treatments and diagnostic tools that will improve patients’ chances of survival.”

Discovery could lead to better melanoma treatment

A Faculty led research team has discovered that immune cells may be responsible for drug resistance in melanoma patients.

Melanoma cellsAlong with colleagues at the Cancer Research UK Manchester Institute, Dr Claudia Wellbrock found that chemical signals produced by immune cells known as macrophages also act as a ‘survival signal’ for melanoma cells. When the researchers blocked this signal – called TNF alpha – melanoma tumours were smaller and easier to treat. The research suggests that targeting this ‘survival signal’ could lead to new treatments. Dr Wellbrock says:

“This discovery shows that immune cells can actually help melanoma to survive. Particularly when patients are receiving treatment, the immune cells produce more of the ‘survival signal,’ which makes treatment less effective. So combining standard treatment with immunotherapy could provide more long-lasting and effective treatments to increase survival.”

Melanoma is the most deadly form of skin cancer with around 13,300 people diagnosed in the UK each year. Rates of the disease have increased more than fivefold since the 1970s. Professor Richard Marais, Director of the Cancer Research UK Manchester Institute, said:

“Melanoma is particularly difficult to treat as many patients develop resistance to standard treatment within a few years. This research provides a key insight into why this is the case. Drugs which block this ‘survival signal’ have already been developed; using these along with standard treatment may be a promising new approach for melanoma patients.”

Scientists find way to target cells resistant to chemotherapy

Paclitaxel treated cellResearch led by Dr Andrew Gilmore has identified a way to sensitise cancer cells to chemotherapy, making them more open to treatment. The study could pave the way for the development of drugs which will target cells that have become treatment-resistant.

The research team made the discovery while exploring the mechanisms behind resistance to chemotherapy drugs like Paclitaxel, used to treat breast and colon cancer. Dr Gilmore said:

“Cells replicate and divide through a process known as mitosis. This process is carefully controlled and if any mistake is made during normal division then the cell undergoes apoptosis – otherwise known as controlled cell death. Failure of cells to complete mitosis correctly can be the start of cancer. We wanted to understand how this failure – delay of cell division – activates apoptosis, and why some cancer cells may be able to avoid being killed.”

The researchers found a protein known as Bid in colon cancer cells and discovered that Bid is turned on as cells prepare to divide. The cells then die if the division takes too long. Cancer cells that are resistant to chemotherapy still turn Bid on, but go through mitosis too quickly for the cell to be killed. The team found that these cells could be made to die if they directly targeted the part of the cell where Bid operates. Dr Gilmore added:

“Our findings demonstrate that Bid plays a central role in mitosis-related cell death.  This could eventually be of huge benefit in a clinical setting and help patients who suffer from advanced stages of colon cancer.”

Researchers find potential new treatment approach for pancreatic cancer

Faculty scientists believe they have discovered a way to make chemotherapy more effective for pancreatic pancreaticcancercellscancer patients. They hope they have now found an effective strategy for selectively killing pancreatic cancer while sparing healthy cells, which will improve the results of treatment. Research leader, Dr Jason Bruce, said:

“Pancreatic cancer is one of the most aggressive and deadly cancers. Most patients develop symptoms after the tumour has spread to other organs. To make things worse, pancreatic cancer is highly resistant to chemotherapy and radiotherapy. Clearly a radical new approach to treatment is urgently required. We wanted to understand how the switch in energy supply in cancer cells might help them survive.”

The study found that pancreatic cancer cells may have their own specialised energy supply that maintains calcium levels and keeps cancer cells alive. Maintaining a low concentration of calcium within cells is vital to their survival and is achieved by calcium pumps on the plasma membrane. These pumps, known as PMCA, are fuelled using ATP, the key energy currency for many cellular processes.

All cells generate energy from nutrients using two biochemical energy ‘factories,’ known as mitochondria and glycolysis. Mitochondria generate almost 90% of the cells’ energy in healthy cells. In pancreatic cancer cells there is a shift towards glycolysis as the major energy source. It is thought that the calcium pump has its own supply of glycolytic ATP, which gives the cancer cells an advantage over normal cells.

Scientists used cells from human tumours and investigated the effects of blocking each energy source in turn. Blocking the mitochondrial metabolism had no effect. However, when they blocked glycolysis they saw a reduced supply of ATP which inhibited the calcium pump. This resulted in a toxic calcium overload and the death of the cell. Dr Bruce added:

“It looks like glycolysis is the key process in providing ATP fuel for the calcium pump in pancreatic cancer cells. Although an important strategy for cell survival, it may also be their major weakness. Designing drugs to cut off this supply to the calcium pumps might be an effective strategy for selectively killing cancer cells while sparing normal cells within the pancreas.””