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The European Cancer Stem Cell Research Institute The story so far

What are cancer stem cells?

Understanding cancer stem cells offers the potential to transform the way we tackle cancer, giving researchers the knowledge needed to investigate new targeted cancer therapies and understand resistance to current gold standard treatments.

Cancer stem cells represent a small proportion of the types of cell found in a tumour. Like all stem cells, they can divide and renew themselves, as well as giving rise to other cell types. Cancer stem cells are resistant to drug and radiotherapy treatments and can spread around the body to seed secondary cancers. Cancer stem cells may be present in a cancer from very early on, but they may also only appear late in the cancer development, which is why early detection and treatment offers better patient outcomes.

When the European Cancer Stem Cell Research Institute was launched, the concept of a cancer stem cell was a relatively new area of cancer research. The Institute’s knowledge of cancer stem cells has grown rapidly since they were established, and their research is contributing to an exciting and expanding area of science that is transforming the way we think about the development and treatment of cancer.

Finding effective treatments against cancer stem cells will fundamentally change the lives of people with cancer. Therapies that target cancer stem cells will not only improve clinical outcomes from early treatment, but will also offer new hope for those who are diagnosed in the later, advanced stages of cancer.

The European Cancer Stem Cell Research Institute aims to understand the biological processes which drive the behaviour of cancer stem cells, and beat the mechanisms which drive the spread of cancer and drug resistance. Their team of researchers plan to develop treatments that target these cancer stem cells, to create more effective cancer therapies, which will have dramatic impacts on the way we prevent, diagnose and treat the disease.

History of the Institute

The European Cancer Stem Cell Research Institute at Cardiff University was the vision of the late Professor Alan Clarke. Alan was fascinated by the relationship between the normal adult stem cells that are vital for sustaining the parts of the body which need to constantly renew their cell content – like the gut, skin and blood – and cancer. He saw parallels between the behaviour of these stem cells and cancers, and cancer stem cells. He foresaw the need for a critical mass of researchers to use advanced biological model systems to understand normal stem cells as the origins of cancer, as a way to improve prevention and early diagnosis, and also to understand how normal stem cell biology can be subverted to generate cancer stem cells. The Institute formally opened its doors in 2013, when it moved into new state-of-the-art purpose-built laboratories in Cardiff University's Hadyn Ellis Building with a full complement of permanent academic staff and junior research fellows. From the very start, the research groups formed a tightly-knit and highly motivated community, driven by their interest in stem cells and cancer.

Professor Alan Clarke was the founding Director of the Institute and it was a huge loss when he suddenly passed away at the end of 2015. Such tragic events inevitably touch lives in many ways, and he is truly missed at the Institute and University.

Professor Matt Smalley becomes Director

Professor Matt Smalley was the first external recruit to the Institute, in 2012, before it even officially launched. Matt had served Deputy Director under Alan Clarke and helped guide the Institute through the troubling period after Alan Clarke’s death.

Matt was appointed as Institute Director at the start of 2018. His first act was to instigate an external review by a panel of high profile UK scientists in order to examine both the science and the strategy of the Institute for the future. The visit was a great success, with the external panel particularly impressed by the quality and enthusiasm of the junior research fellows and supported Professor Smalley’s vision for closer clinical links while still supporting basic research.

The Institute has gone from strength to strength, with great successes in funding, research and recruitment. The European Cancer Stem Cell Research Institute has recently appointed a new lecturer, Dr Toby Phesse, an expert on gastric cancer.

Since the beginning of 2018, the Institute has secured >£2.6 million of funding awards, to support the world-leading research of its junior fellows.

Recent funding successes

Catherine Hogan has been awarded £372,338 over 36 months by the Cancer Research UK early detection committee for her project Unravelling mechanisms of cell competition in pancreatic cancer initiation. Potential novel targets for early detection.

Catherine Hogan

“The pancreas is composed of multiple cells types, each with a distinct function that either regulates blood sugar levels or contributes to the digestion of food. This organ is highly changeable, meaning that every cell within its tissue has the potential to reprogramme to become another cell type. This reprogramming is triggered by damage or disease of the organ, including in cancer. Our research is focused on understanding the very first stages of pancreatic cancer and how changes within cells can lead to the initiation of cancer development.

"We switch on the cancer-causing genes in cells, and then monitor the relationships between the cancer-causing cells and the normal cells around them. This will enable us to achieve a better understanding of the earliest stages of pancreatic cancer, which will lead to improved detection methods and the creation of new diagnostics.”

Gastric cancer is the third most common cause of death due to cancer worldwide, with approximately 700,000 cases diagnosed annually. A recent MRC project grant has allowed Toby Phesse to investigate the therapeutic benefit of targeting a receptor called Frizzled that transmits signals via a pathway called Wnt. This grant utalises an industrial partnership with Oncomed Pharmaceuticals to enable the Institute to perform pharmacological and genetic experiments to discover new therapies for gastric cancer.

Toby Phesse with his team Chloe Austin (PhD student), Sarah Koushyar and Valerie Meniel (Postdoctoral Scientists)

"My research is interested in how cell signalling regulates cell function in normal tissue, stem cells and tumours to gain insight into how cancer is initiated, grows and spreads. We then use this information to identify novel targets and strategies to treat various cancers, with a focus on the Wnt signalling pathway and gastrointestinal and prostate."

Inaccuracy of initial tests for colorectal cancer are putting patients at unnecessary risk, highlighting vital need for the development of precise and non-invasive testing. A grant of over £400,000 is helping Dr Lee Parry and his team at the European Cancer Stem Cell Research Institute to bring these closer to a reality.

Lee Parry

"Fifty percent of colorectal cancer cases are preventable. We are investigating how diet, gut bacteria and environmental impacts on intestinal stem cells, which are the cells that originate colorectal cancer. By understanding the behaviour of these cells, we can improve prevention, diagnosis and treatment of this type of cancer.

“We believe that we can use a biological agent called SL7207 to detect whether colorectal cancer cells are present. We can administer this agent and if this is persistently present in the faecal testing, this is indicative of pre-cancerous colonic polyps."

Florian Siebzehnrubl has been awarded £626,494 by the Medical Research Council to investigate how a protein called FGF2 influences different types of glioblastoma cells within a given tumour.

Florian Siebzehnrubl

"We are researching the way in which FGF2 affects these different types of glioblastoma cells in different ways, with some becoming more aggressive in direct response to FGF2. By understanding the function of FGF2 and its receptors, we can get a better understanding of the aggressive nature of glioblastoma and use this to help with the development of new treatments. This will help us to focus more targeted drugs at these specific receptors, and importantly, provides a means of predicting which patients would benefit most from this therapy."

Research discoveries

Fat is powering tumour growth in brain cancer. The Institute gained a valuable insight into what fuels slow and fast dividing cancer cells, unveiling the potential to target aggressive brain cancer more effectively. Glioblastoma is the most common and aggressive form of brain cancer in adults, and this disease currently has no known cure. Understanding the behaviour of the cells in this form of cancer is vital in developing effective treatments.
The Institute shed light on the link between skin cancer development and kidney transplants, highlighting the importance for clinicians to monitor transplant patients for these virus-induced cancers. In patients who lack the protection of their immune system, viruses like HPV can spread and cause cancer unchecked. This means that those receiving a kidney transplant, who receive drugs to suppress their immune system as part of their treatment, are left open to cancer-causing viruses like HPV.
Institute scientists have uncovered a protein which can drive aggressive breast cancer, and may be a target for new and improved therapies. There are over 11,000 deaths caused by breast cancer each year in the UK, but their research has discovered new information about the underlying mechanisms of aggressive breast cancer, which could potentially influence future therapies for the disease.

Collaborative ethos

Collaboration is essential to effectively tackling cancer.

The European Cancer Stem Cell Research Institute is supported by, and works with, many groups in the pursuit of a better future for cancer patients. Members of staff are funded by, or working on grants awarded by, organisations such as:

  • Breast Cancer Now
  • Breast Cancer Research Aid
  • Cancer Research UK
  • Cancer Research Wales
  • Medical Research Council
  • Prostate Cancer Research Centre
  • Prostate Cancer UK
  • Ser Cymru/Welsh Government
  • Tenovus Cancer Care
  • The European Union
  • Wales Cancer Research Centre

Future plans

The Institute is entering a very exciting period, building on its funding successes and great advances in its knowledge of stem cells, cancer and cancer stem cells. The European Cancer Stem Cell Research Institute will also continue to build on contacts with its clinical colleagues, to not only host junior clinicians in our laboratories to carry out their research but also through dialogue with senior oncologists in South Wales, the West of England and throughout the UK and internationally. Through this, they will be able to advance the Institute’s discoveries, bringing them closer to the clinic, whilst also understanding the real clinical problems encountered on a daily basis and work to help solve them.

The timeline of the European Cancer Stem Cell Research Institute spans a period of profound change in our understanding of the field of stem cells and cancer as this sector of cancer research has developed. It was founded when this area of science was novel and it has played a pivotal role in establishing this area of science in the field of cancer research. The quality of the research at the Institute is reflected by its growth and research success, which has continued to strengthen the Institute as a centre of excellence for this area of cancer research.

The future of the Institute is exciting, as their research continues to transform the way we treat cancer and bring the concept of targeted therapies for cancer stem cells closer to a reality.

Credits:

Created with images by Drew Hays - "Scientist with a Petri dish" • kkolosov - "analysis biochemistry biologist" • David Clode - "Glowing coral garden" • kalhh - "head magnetic resonance imaging mrt" • GreenFlames09 - "Kidney Model 7" • marijana1 - "pink ribbon pink ribbon"

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