Bowel Cancer Breakthrough May Benefit Thousands of Patients
Researchers at Queen’s University have made a significant breakthrough that may benefit patients with bowel cancer.
Dr Sandra van Schaeybroeck and her team have discovered how two genes cause bowel cancer cells to become resistant to treatments used against the disease. The research, which was funded by Cancer Research UK, was published this month in the prestigious international journal Cell Reports.
The activity of the two genes, called MEK and MET, was uncovered when the researchers looked at all the different pathways and interactions taking place in bowel cancer cells.
Dr van Schaeybroeck and her group found that these bowel cancers switch on a survival mechanism when they are treated with drugs that target faulty MEK genes. But when the researchers added drugs that also block the MET gene, the bowel cancer cells died. The team are now testing a new approach to target these two genes in the most aggressive forms of bowel cancer in a European Commission funded clinical trial that is being led by Dr van Schaeybroeck.
Currently over 40,000 people are diagnosed with bowel cancer in the UK each year and over 16,000 patients die of the disease. More than half of patients develop the aggressive form of the disease which does not respond to standard therapy, the five year overall survival in this patient group is less than five per cent.
Study author Dr Sandra van Schaeybroeck, from the Centre for Cancer Research and Cell Biology (CCRCB) at Queen’s University, said: “We have discovered how two key genes contribute to aggressive bowel cancer. Understanding how they are involved in development of the disease has also primed the development of a potential new treatment approach for this disease.”
Queen’s University Vice-Chancellor, Professor Patrick Johnston, said: “Understanding the genes that cause bowel cancer is a key focus of our research. Our discoveries in this deadly disease have identified a new route to clinical application for cancer patients.”
Professor David Waugh, Director of the CCRCB at Queen’s, said: “The publication of this research by Dr van Schaeybroeck and her team demonstrates our commitment to performing excellent science here in Belfast that can be directly translated to the clinic.”
The clinical trial, which is called MErCuRIC and is due to start in September, will deliver personalised medicine to Northern Irish patients and patients from other European countries. Overall, the pan European collaborative effort will involving 13 research/clinical teams from nine European countries.
Scientists at the Centre for Cancer Research and Cell Biology have been awarded a £126,000 grant by blood cancer charity Leukaemia & Lymphoma Research for research to improve treatments for blood cancer patients.
The two year research project will be led by Professor Ken Mills, Dr Kienan Savage, Professor Mary Frances McMullin and Dr Fabio Liberante. They will develop new treatments that are more effective at seeking out and destroying abnormal white blood cells.
The research will focus on a genetic fault found in patients with myelodysplastic syndrome (MDS). MDS is a group of blood disorders where the balance of healthy blood cells in the body is disrupted by the growth of ‘master’ cells. Patients with these types of disease are usually elderly and are often unable to cope with intensive treatment like chemotherapy.
Professor Mills said: “Several genetic abnormalities have been connected with MDS but we don’t know their role in the onset or progression of the disease. In particular a gene called SF3B1 is known to be mutated in the blood cells of around a third of patients with MDS. As many as 85% of patients with a type of MDS called refractory anaemia with ring sideroblasts (RARS) have the error. The ultimate aim of our research is to improve treatment for patients with MDS, particularly RARS, by identifying a specific drug that can target this SF3B1 mutation.”
The researchers will study this particular genetic fault and use cutting-edge genetic techniques to identify exactly how the mutated SF3B1 gene influences the development of MDS. They will look at how the abnormal SF3B1 affects the ability of the cell to repair damaged DNA, how this impairment influences disease progression, and whether it’s possible to block it with drugs.
Dr Matt Kaiser, Head of Research at Leukaemia & Lymphoma Research, said: “The majority of patients diagnosed with MDS are over the age of 60 and most are unable to cope with the current treatments available. This research shed light on how a genetic error in SF3B1 affects blood cell development and behaviour. Improving treatments and tailoring them to target specific rogue cells will enable a safer and more effective way of combating the disease for patients.”
Dr Kienan Savage
Cancer researchers at Queen’s University Belfast have made a breakthrough which could signal new treatments for women at high risk of breast and ovarian cancer.
Currently around one in 1,000 women in the UK carry what is known as a BRCA1 mutation - the same condition that prompted well-known actress Angelina Jolie to undergo a double mastectomy. They have up to an 85 per cent risk of developing breast cancer, and up to 40 per cent risk of developing ovarian cancer, in their lifetimes.
Until now, preventive surgery - mastectomy (breasts) and oophorectomy (ovaries) - has been the only way of reducing the risk of developing both types of cancers.
The new discovery by researchers in Queen’s Centre for Cancer Research and Cell Biology (CCRCB) may mean women affected with BRCA1 could use drugs, which are already available, to reduce their risk of developing the disease, rather than undergo irreversible surgery. In turn, such treatments would open up the possibility of some of these women, who might otherwise have an oophorectomy, still being able to have children.
The new research by Dr Kienan Savage and Professor Paul Harkin at CCRCB proves there is a direct link between high levels of oestrogen and DNA damage, which causes cancer, in the breasts and ovaries. Specifically, the scientists discovered that the cells of women with the BRCA1 mutation cannot effectively fight the very high levels of oestrogen that exist in all women’s breasts and ovaries, leaving them vulnerable to DNA damage. While this link between oestrogen, breast/ovarian cancer and BRCA1 mutation has been suspected by the scientific community for years, it has not been proven until now.
Dr Kienan Savage, from the CCRCB, and who led the research, said: “This discovery is very significant in the management of women with the BRCA1 gene mutation. It’s the first really credible evidence that oestrogen is driving cancer in women with a BRCA1 gene mutation. Because of this discovery, we now have the opportunity to propose an alternative treatment to surgery. It also opens up the possibility of pausing treatment for a period in order for women to have children, if desired.
“What also makes this exciting is that there are drugs already on the market which turn off oestrogen production. In theory, we could use these drugs to chemically reduce oestrogen production in women which could negate the need for irreversible surgery.”
The Queen’s-led research, which has been ongoing for four years, was carried out with funding from Cancer Focus NI and Cancer Research UK. It is carried in the latest edition of the prestigious USA-based journal Cancer Research.
Professor David Waugh, Director of the Centre for Cancer Research and Cell Biology at Queen’s, said: “This breakthrough by researchers at CCRCB is great news for women with the BRCA1 gene and the cancer research community as a whole. It is pivotal in that it reveals more about the mechanisms behind breast and ovarian cancer.
“This work of Dr Kienan Savage and Professor Paul Harkin is further example of the world-leading research being undertaken at Queen’s which continues to advance knowledge and change lives.”
Roisin Foster, Chief Executive, Cancer Focus Northern Ireland, said: “Cancer Focus is delighted to fund this ground-breaking research into breast cancer, which has the potential in the forseeable future to benefit women all over the world. We are only able to support this vital work because of the generosity of our local community.”
The researchers are currently seeking funding to launch clinical trials and hope to do so within 12 months. It is envisaged that, in the first instance, a small control trial will be carried out using a combination of two drugs on 12 women for a period of three months, using biopsy, blood and urine samples to track DNA damage.
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Pictured L to R: Patient Allister Murphy with Professer David Waugh and Professor Joe O'Sullivan
Queen’s University Belfast has announced it is to partner with the University of Manchester to form the first regional Movember Centre of Excellence in the fight against prostate cancer.
The radical development is in partnership with Prostate Cancer UK and the Movember Foundation and will see an investment of £5 million over a five-year period across Belfast and Manchester.
Prostate cancer is the most common cancer among males in the UK with 40,000 new diagnoses every year. Comprising an outstanding team of internationally recognised scientists from across different disciplines, the key focus of the Belfast-Manchester hub will be improving outcomes for men with advanced disease. The funding will ensure that lab breakthroughs are translated into clinical benefits as quickly as possible. The Belfast-Manchester nexus will also include the Manchester-based Christie NHS Foundation Trust, the largest single-site cancer centre in Europe. A second Centre of Excellence will be located in London and will also receive £5 million over five years.
The two Centres were selected after a rigorous, international peer-review process. To qualify for funding, lead scientists had to prove strong, international track records and their teams needed to demonstrate existing or planned cross-discipline collaborations between basic and clinical scientists.
Over the five-year programme, researchers in Belfast and Manchester will identify men at high risk of aggressive disease, and find which patients respond best to various treatment options – an approach often referred to as ‘personalised medicine’. Cancer specialists will also work on refining new and existing treatments such as radiotherapy to improve how well they work for advanced prostate cancer, including cancer that has spread to the bones. The Belfast-Manchester Centre will bring in expertise from outside of prostate cancer, using insights from the latest research into other cancers including melanoma, breast and lung.
Professor David Waugh, Director of the Centre for Cancer Research and Cell Biology at Queen’s, is one of two Scientific Co-Directors of the Centre, alongside Professor Richard Marais, Director of the CRUK Manchester Institute.
Prof Waugh said: “The Belfast-Manchester Centre of Excellence provides a rare opportunity to bring together an international team of experts in radiation, biomarker discovery, genetic modelling and tumour biology who will use their individual talents in a collective and focused manner to make significant discoveries to benefit and extend the lives of men with prostate cancer.
“The scale and duration of funding available through the programme enables clinicians and scientists to tackle major clinical problems and more importantly, the longer timeframe also enables the team to ensure that our scientific progress has a clear clinical line-of-sight, and that we can begin to apply this new knowledge into clinical practice – resulting in more immediate benefits for those affected.
“I am extremely excited about what we can achieve.”
Professor Joe O’Sullivan, chair of radiotherapy development and clinical lead for radiotherapy at the Northern Ireland Cancer Centre and Chair of the Uro-Oncology Multidisciplinary Team at the Belfast Trust will be one of two Clinical Co-Directors of the Centre.
Prof O’Sullivan said: “I am extremely excited about the prospect of working with a team of world class researchers and those who are bringing their expertise from outside prostate cancer research in to the field for the first time.
“Through this research programme we have the opportunity to increase the speed of clinical advances by taking a fresh approach to prostate cancer research involving state of the art technology and a genuine collaborative approach.”
Movember UK Country Manager Sarah Coghlan said the Centres of Excellence scheme was “one of the most significant and exciting milestones for the Movember Foundation and prostate cancer research in the UK”.
She continued: “We’re bringing the best in the research world together for a sustained period to have a real impact and to develop real understanding of how to fight this disease.
“These Movember Centres of Excellence are the first of their kind in the UK focussed on prostate cancer and they represent the Movember Foundation’s commitment to having an everlasting impact on the face of men’s health. We salute every one of the Mo Bros and Mo Sistas in the UK. This wouldn’t be possible without them.”
In addition to the funding from Movember, the HSC R&D Division of the Public Health Agency has contributed an additional £500,000 to the Centre. It will be used to fund two key posts within the Northern Ireland Cancer Centre – a research radiographer and a post-doctoral research scientist.
Dr Janice Bailie, Assistant Director of the HSC R&D Division at the Public Health Agency said: “I am delighted that we will partner with Movember/Prostate Cancer UK to support the Belfast arm of this new Centre of Excellence in translational prostate cancer research.
“I believe this project has the potential to bring significant benefits to those living with prostate cancer in Northern Ireland and beyond. The Movember award recognises the strong track record in prostate cancer research in Belfast and Manchester, and this investment from HSC R&D Division will further enhance the already close working relationship between the Northern Ireland Cancer Centre in Belfast Health and Social Care Trust and the Centre for Cancer Research and Cell Biology at Queen’s University Belfast.” Professor Richard Marais of the CRUK Manchester Institute, part of the University of Manchester, said: “We have established a unique collaboration that will bring together knowledge and insights from across different cancers and disciplines, which will enable us to tackle some of the complexities still surrounding this disease from a new perspective.
“Crucially, by working in partnership we also hope to increase the speed at which lab breakthroughs reach the man in the clinic and have a direct impact on patient outcomes.”
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