Projects starting from June 2012 to June 2015
Grant Holder: Professor Mark Pritchard
Institution: University of Liverpool, England
Grant Award: £198,467.00 for 2.75 years
Project Title: How does the reduction in stomach acid help progression of cancer?
Stomach cancer is a common and life-threatening disease, which nearly always develops in people who have had a long-term infection with a bacterium called Helicobacter pylori. One of the pre-cancerous stages of the disease is called ‘atrophy’ which destroys some of the acid-producing cells in the stomach. As a result, the pH within the stomach becomes higher than normal, making it less acidic and more alkaline (known as hypochlorhydria). Studies in mice have shown that this elevated pH allows other microorganisms, such as bacteria, to start growing in the stomach, where they would not normally survive. It is believed that the presence of these bacteria contributes to the development of cancer within the stomach. Curiously, however, long-term use of acid-suppressing drugs does not have the same effect. Professor Pritchard is therefore going to use his new AICR grant to study the stomach environment in mice that develop cancer following Helicobacter pylori infection, in the hope that the studies will identify molecules that indicate those people who are more likely to develop cancer. If he identifies such molecules, these could be used to develop a better screening programme for patients who may be at risk of developing stomach cancer.
Grant Holder: Professor Adrian Whitehouse
Institution: University of Leeds, England
Grant Award: £178,323.00 for 3 years
Project Title: Investigating new treatments against Kaposi’s sarcoma-associated herpesvirus
Several viruses are known to cause cancers. One such virus is Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV is the cause of Kaposi’s sarcoma (KS), which is a type of cancer that is often associated with skin lesions, as well as two other diseases. KS is often associated with AIDS, and with the prevalence of AIDS in Africa being so high, it is now the most commonly reported adult tumour in sub-Saharan Africa. There are currently no vaccines or antiviral treatments against KSHV. The virus multiplies and spreads throughout the body by bursting the human cells (called lytic replication) in which they are living. This mechanism plays a big role in causing disease and tumour growth. Researchers therefore want to aim new treatments at stopping lytic replication. Professor Whitehouse will be using his AICR grant to study proteins that are involved in the spread of the virus, with the aim to find a way of blocking virus spread, and thereby stopping development of KS.
Grant Holder: Dr Khuloud Al-Jamal
Institution: King’s College London, England
Grant Award: £197,494.00 for 3 years
Project Title: Using nanocapsules to improve efficiency of radiotherapy
Radiotherapy is one of the main forms of treatment against cancer. High energy rays are directed to the cancer-affected area in order to destroy the cancerous cells, in an attempt to cause as little damage as possible to healthy cells. However, when the beams are fired at the tumour from outside the body they need to pass through the healthy tissues that surround the tumour first. Several other mechanisms for delivering radiotherapy are being tested that could be much more effective than the current method. Nanocapsules (small capsules that are one-thousandth the size of a human hair) that can be filled with small doses of therapeutic radioactive particles are being tested to see if they can kill tumour cells. Nanocapsules are also being tested for the transport of other particles, such as drugs to treat other diseases. With her new AICR grant, Dr Al-Jamal will test whether small molecules, called siRNAs, which are thought to make cancer cells more susceptible to radiotherapy, can be delivered to tumours at the same time as the radioactive particles, using the nanocapsules. If successful, this new technique could reduce the toxic effects of radiotherapy in healthy tissues, and the side effects that patients experience.
Grant Holder: Professor Amparo Cano
Institution: Instituto de Salud Carlos III, Madrid, Spain
Grant Award: £206,813.00 for 3 years
Project Title: Understanding the role of LOXL2 in the development of skin and breast cancer
One of the main factors making tumours so dangerous is their ability to invade surrounding tissues and organs and spread throughout the body. This is known as metastasis. Individual cancer cells squeeze between the normal cells nearby and push their way through the tissue. They are then carried in the blood stream and can form new tumours in other parts of the body, known as secondary tumours or metastases. In the last decade, significant findings have shed some light on the processes that enable cancer cells to spread. This involved the identification of key molecules for tumour spread. Professor Cano’s research team have previously described the interactions of some of these molecules with a molecule called LOXL2. She will be using her new AICR grant to reveal the role of a molecule called LOXL2 in tumour development and metastasis. The work will mainly focus on breast and skin tumours.
Grant Holder: Professor Kairbaan Hodivala-Dilke
Institution: Queen Mary University of London, England
Grant Award: £260,803.00 for 3 years
Project Title: Using blood vessel formation within tumours as a way to stop cancer growth
In order for tumours to grow larger than about 1 millimetre across they must have their own blood supply to enable enough oxygen and nutrients to reach the cells. The tumours therefore make new blood vessels, from existing ones, which specifically bring food and oxygen to the cancer cells. This process is called angiogenesis. If it is possible to stop this from happening or blocking the blood flow into tumours, this is a possible way to try to stop the cancer. Professor Hodivala-Dilke’s research group is studying some of the molecules involved in angiogenesis, and they have promising findings that show a possible new way to efficiently stop tumour growth. With her new AICR grant, she wants to test the effectiveness and safety of these methods, alongside chemotherapy, with the hope that these methods will one day be used to treat human cancer.
Grant Holder: Professor Jamie Rossjohn
Institution: Monash University, Melbourne, Australia
Grant Award: £202,034.00 for 3 years
Project Title: Investigating the role of immune system cells in cancer
The immune system constantly monitors the body for signs of anything that may cause disease, including cancer. White blood cells are the main cells that run the immune system, and one type of white blood cell is called a natural killer (NK) cell. These cells have molecules on their surface, called receptors, which recognise viruses or tumour cells. There are several such receptors, and they are involved in switching on, or waking up, NK cells when the body comes under attack. The genes that control these receptors have been shown to influence how patients react to treatment. Some specific genes appear to have a big effect on the outcome of patients who have received a stem cell transplant to treat a type of cancer called acute myeloid leukemia (AML). Patient outcomes were dependent on the types of genes that different patients had. With his new AICR grant, Professor Rossjohn is planning to study the structure of these NK cells receptors and how they interact with other molecules, in order to learn how they recognise tumour cells. These results will hopefully help to reinterpret results from stem cell transplant patients so that in future better matches can be found when selecting stem cell donors for diseases that affect the blood or bone marrow, such as AML.
Grant Holder: Professor Malcolm Dunlop
Institution: University of Edinburgh, Scotland
Grant Award: £235,063.00 for 3 years
Project Title: Investigating the genes involved in age-related cancer risk in Lynch Syndrome
When people talk about a person’s risk of developing cancer, genes are often a factor. Sometimes it is only one specific gene that makes the difference, other times it is many small changes to lots of genes. DNA is constantly being unzipped and copied in order to produce millions of new cells each day, but this means that there are many opportunities for the biological assembly line, which makes new DNA, to be broken. This is called mismatch, like a shirt where the buttons are not lined up; the result is not the same as when the shirt is buttoned up correctly. A series of genes exist to fix these mismatches. Lynch Syndrome is a disorder where the genes that normally fix these mismatches are no longer able to do their job. People who have Lynch Syndrome are much more likely to get cancer, but the age at which this happens varies greatly from one person to the next. While people with Lynch Syndrome experience extensive surveillance to catch potential cancers early, both the patients and healthcare professionals would benefit if it was possible to predict at what age people would be more likely to get cancer. Professor Dunlop has collected samples from a large group of people who suffer from Lynch Syndrome and will use his AICR grant to test for genes that could control the age at which people might develop cancer. This will also be compared with samples from the general population and be used to develop age-specific risk prediction, to be used for the clinical management of Lynch Syndrome.
Grant Holder: Professor Tony Carr
Institution: University of Sussex, Brighton, England
Grant Award: £221,557.00 for 3 years
Project Title: Studying yeasts to identify new human targets for chemotherapy?
Hydroxycarbamide is a drug that stops cells from making and repairing DNA, it affects a molecule called RNR. It is used as a common treatment in cancers that cause the abnormal growth of blood cells in the bone marrow, for example acute myeloid leukemia (AML). In AML it helps to reduce the number of cancerous cells but the disease cannot be controlled for very long, as resistance to the drug often occurs. The use of hydrocarbamide against other cancer types is also being investigated, but until now little is known about how it stops cancer cells from growing or how they become resistant to the drug. In yeasts, two mechanisms that control RNR have been identified and are widely known. Now new research carried out by Professor Carr, also in yeast, has revealed a possible third mechanism. His AICR grant will be used to study how these three mechanisms work and attempt to find equivalent human molecules that could control RNR. This would potentially identify new molecules that could be turned on or off for use in chemotherapy.
Grant Holder: Dr Michael Hauptmann
Institution: The Netherlands Cancer Institute, Amsterdam, The Netherlands
Grant Award: £236,108.00 for 3 years
Project Title: What is the risk of leukemia in children and young adults following radiation exposure from computed tomography?
Computed tomography (CT scan) is a type of medical scan that takes a series of x-rays from different angles of your body. These appear as ‘slices’ of a part of your body, and these slices can be put together to give a very detailed image of the inside of your body. The CT scan delivers much higher doses of radiation than most other imaging techniques which are used to detect or diagnose ailments. This is why doctors only use them when there are no alternatives, and the benefits greatly outweigh the risks. There has been a large increase in the use of CT in the last 10-15 years. As a result, radiation protection, especially among children needs to be monitored and reviewed. Children are particularly sensitive to radiation-induced cancer, and have a long life ahead of them in which to express possible side effects, such as an increased risk of leukemia. 57 million CT scans were carried out in the US in 2007. It is estimated that these scans can be linked to 29,000 cancers occurring in those patients’ lifetime, of which more than 4,000 are from CT scanning during childhood. Dr Hauptmann will use his AICR grant to look at the records of Dutch childhood CT scans and compare them to the Netherlands Cancer Registry to study whether there is a potential link. These results will contribute to a European study investigating risk for rarer forms of cancer. Dr Hauptmann’s study will thereby provide safety information for this invaluable method, as well as contributing to our knowledge of childhood and young adult leukaemia and risks associated with low-dose radiation.
Grant Holder: Dr Cameron Bracken
Institution: Centre for Cancer Biology, Adelaide, Australia
Grant Award: £189,186.00 for 3 years
Project Title: What is the role of microRNAs in Epithelial-Mesenchymal Transition?
One of the main factors that makes tumours so dangerous is their ability to invade into surrounding tissues and organs and spread throughout the body, known as metastasis. Individual cancer cells squeeze between the normal cells nearby and push their way through the tissue. They are then carried in the blood stream and can form new tumours in other parts of the body, known as secondary tumours or metastases. Around 90% of deaths associated with solid tumours are caused by secondary tumours. It is therefore important to fully understand how metastasis occurs. One of the main ways cancer cells move involves a method called EMT (Epithelial-Mesenchymal Transition). Epithelial cells are immobile cells that cover the surfaces within the body. EMT involves genes inside epithelial cells to ‘reprogramme’ so that they turn into another type of cell, called mesenchymal cell, which is capable of pushing through tissues and moving to other places around the body, where new tumours can form. MicroRNAs are small molecules that help to control our genes by acting as off switches. Some of these microRNAs appear to play a role in cancer, and they are believed to play a big part in EMT. Dr Bracken will use his AICR grant to study how microRNAs are involved in EMT and how this applies to human tumours.
Grant Holder: Professor Tony Tiganis
Institution: Monash University, Melbourne, Australia
Grant Award: £273,118.00 for 3 years
Project Title: Studying the link between obesity and liver cancer
Primary liver cancer is the sixth most common cancer in the world. Most liver cancers start after cancer cells have spread from a different part of the body, this is called secondary cancer. Primary liver cancer, where the liver is the first place that the tumour grows, is one the third most common cause of death from cancers worldwide, and survival rates are very low. Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, accounting for 90% of cases. HCC is more common in developing countries, where it is associated with long term Hepatitis B infection. HCC has almost doubled in the US & nearly tripled in Australia in the last 20 years, and the obesity epidemic is believed to play a large part in this drastic increase. Professor Tiganis will be using his new AICR to study the molecular changes that happen within the liver as a result of obesity, and how these molecular changes can lead to HCC.
Project Title: Professor Brian Gabrielli
Institution: Diamantina Institute, University of Queensland, Brisbane, Australia
Grant Award: £239,467.00 for 3 years
Project Title: Investigating new mutations in melanoma
Melanoma is the most dangerous type of skin cancer that is often associated with exposure to the sun or sunbeds. It is one of the most common causes of cancer in people aged 15-44, although incidences of the disease increase steadily with age. Professor Gabrielli will be using his AICR grant to study new genome mutations that have been associated with melanoma. The genome consists of all the information that is needed to build and maintain a living organism. Advances in technology has allowed for more and more entire genomes to be studied, and increasing numbers of mutations are being identified in the 50 cancer genomes that are currently being analysed worldwide. Many of the mutations are uncommon, and therefore researchers are unsure of whether they play a role in cancer formation. The project will involve analysis of 250 new mutations that are found in melanomas, to identify those that directly lead to disease occurrence.
Grant Holder: Professor Eduard Batlle
Institution: IRB-Institute for Research in Biomedicine, Barcelona, Spain
Grant Award: £234,876.00 for 3 years
Project Title: Learning how bowel stem cells develop into tumours
All normal tissues within our bodies have a tiny population of stem cells. Stem cells are a kind of 'starter cell' which can multiply and change into a wide variety of other cells depending on where they are located in the body. Stem cells from the bowel have been isolated in order to study their role in bowel cancer, thanks to a molecule on the surface of these stem cells. This molecule can also be found within the tumour in bowel cancers. Professor Batlle and his research group have recently discovered that the types of genes that can be found in bowel stem cells predict whether patients with bowel cancer will relapse after treatment. These results point towards a link between bowel stem cells and bowel cancer. With the new AICR grant Professor Batlle will analyse and compare normal bowel stem cells and bowel cancer stem cells to learn how new tumours occur after treatment, or when it spreads to different parts of the body.
Grant Holder: Dr Simon Cook
Institution: Babraham Institute, England
Grant Award: £194,819.00 for 3 years
Project Title: FGFR-dependent tumour cells and how they develop resistance
Researchers are increasingly interested in a group of proteins called FGFRs as a means to treat cancer. The FGFR proteins normally give instructions to cells to survive and grow, and they also play an important part in healing wounds. However, the FGFR proteins can also help tumour cells to grow in several cancer types, including breast, stomach, and bladder cancer, as well as multiple myeloma. In these cancers, FGFR proteins are either mutated or they can be found in much higher quantifies than normal. Cells within these tumours become ‘addicted’ to FGFR proteins, needing them to survive and grow. This represents the tumours’ ‘Achilles’ heel’ and researchers are trying to develop treatments that block the FGFR proteins in the hope that this will also stop cancer growth. Dr Cook and his research team have identified stomach, bladder, and breast cancer cells that need FGFR to multiply or survive. The growth of these tumour cells is blocked by new drugs that are able to stop FGFR proteins delivering signals that tell tumours to grow. He will use his AICR grant to investigate the mechanisms that cause the growth and multiplication of breast and stomach cancer cell lines that are addicted to FGFR proteins, and how those mechanisms respond to new drugs that block FGFR, and will aim to identify the genes that are involved in resistance to the drugs; such genes might be useful for developing new drugs in the future.
Grant Holder: Professor Kevin Ryan
Institution: Beatson Institute for Cancer Research, Glasgow, Scotland
Grant Award: £194,499.00 for 3 years
Project Title: Studying a new mechanism that makes tumours resistant to drugs
Chemotherapy drugs are used to kill cancer cells. Drug treatments don’t always work because some cancers become resistant to drugs. They are resistant because cancer cells have molecules on their surface, called drug transporters, that basically ‘spit out’ the drugs from inside the cell, where the drug would normally kill it. Healthy cells also have drug transporters, but in tumours there are many more. So far, scientists have identified three main drug transporters that are involved in chemotherapy resistance. Unfortunately, they do not know why there are so many more drug transporters on cancer cells compared to healthy cells. Professor Ryan and his team have identified a protein within tumours that controls the growth of these drug transporters, and that this protein can prevent cancer cells from being killed by chemotherapy drugs because of drug transporters on the cells. With this AICR grant, they want to further investigate how this protein controls drug transporters and how it is linked to human cancer.
Grant Holder: Professor David Edwin Thurston
Institution: King’s College London, England
Grant Award: £195,200.00 for 3 years
Project Title: New NF-kappaB treatments against blood cancers
In some types of leukaemia, the cancer cells produce a protein call NFkB (pronounced “N-F-kappa-B”) which is known to block the suicide mechanism (called “apoptosis”) normally found in cells. The suicide mechanism is important, as it causes damaged cells to die. This process is often defective in cancer cells, allowing them to escape death and continue to grow, thus leading to cancers. NFkB has also been linked to cancer cells becoming resistant to chemotherapeutic drugs. By directly stopping NFkB, it may be possible to turn the suicide mechanism in cancer cells back on, thus making existing chemotherapy drugs more effective. Professor Thurston will be using his AICR grant to design and test small drug-like molecules that might be able to block NFkB, and this may lead to potential new treatments for blood and bone marrow cancers, and make existing treatments more effective. Molecules that show promising results will be further tested in human tumour models to identify a possible drug candidate to be tested as a new anticancer treatment.
Grant Holder: Dr Stephen Hart
Institution: University College London, England
Grant Award: £173,708.00 for 2 years
Project Title: Developing new treatments for neuroblastoma through the presence of MYCN
Neuroblastoma is a cancer that affects children, usually before they are 5 years old. It is a very rare disease compared to many cancers – only about 100 children are diagnosed each year in the UK. Neuroblastoma is a type of cancer that develops from the cells that are left over from the child’s development in the womb. MYCN is a gene that is well known to be involved in neuroblastoma growth. Many neuroblastoma tumours have too many copies of the MYCN gene, which is referred to as MYCN amplification, and this has been linked to a more aggressive form of the disease. Dr Hart is using his AICR grant to develop a new way of specifically treating neuroblastoma tumours by attacking them through MYCN. He has developed a molecule that can block the MYCN gene, and he will investigate new technology to get this molecule into tumour cells effectively, by wrapping the molecule up in a tiny capsule of fat and protein. If this way of delivering the molecule works, it might also prove a useful way to deliver other types of drugs to treat different cancer types.
Grant Holder: Professor Sibylle Mittnacht
Institution: University College London, England
Grant Award: £200,576.00 for 3 years
Project Title: Investigating the role of checkpoint activation in cancer resistance to radiotherapy
Healthy cells grow and divide in a highly organised and tightly controlled manner in a process called the cell cycle. The cell cycle is made up of several phases, one of which is called G1. Healthy cells have very complex mechanisms to control this process, and when a cell’s DNA is damaged, an emergency signal is released, to stop the cell cycle from going any further. This is known as a checkpoint, and ensures that the DNA damage is repaired (checkpoint activation), and prevents the cells from dying as a result. Unfortunately, cancer cells also have these cell cycle checkpoints. This can affect the way that cancer cells respond to treatments such as radiotherapy, which rely on damaging DNA to kill cancer cells. By understanding the signals involved in checkpoint activation, it might be possible to identify better ways of designing treatments like radiotherapy to prevent cancer cells being able to repair themselves. Professor Mittnacht and her lab have identified several proteins involved in checkpoint signalling, including a protein called STK4. They believe that this protein may be involved in checkpoint activation in cancer cells following radiation (radiotherapy). She will be using her AICR grant to further investigate the role of STK4 in checkpoint activation following radiation, and in cancer cell survival after radiotherapy.
Grant Holder: Professor Ruud Delwel
Institution: Erasmus Medical Center, Rotterdam, The Netherlands
Grant Award: £193,399.00 for 3 years
Project Title: Can Acute Myeloid Leukemia be treated via the EVI1 gene?
Acute Myeloid Leukemia, or AML, is a cancer that affects some of our white blood cells. A gene called EVI1 appears to play a role in the development of AML, as well as some other cancers, including ovarian cancer. By genetically removing EVI1 from cells in the lab it was possible to kill AML tumour cells that normally have the EVI1 gene. It is not possible to cut the EVI1 gene out of the cancer cells in a person with AML, but it might be possible to design treatments that stop the EVI1 gene from working. Professor Delwel wants to use his new AICR grant to stop EVI1 from working in AML by preventing the gene from interacting with other proteins. His research group have previously identified some of these proteins. They now want to learn more about how these interactions work, whether they can be stopped, and whether these interactions have an effect on other genes that might play a role in cancer.
Grant Holder: Professor Randolph Noelle
Institution: King’s College London, England
Grant Award: £169,416.00 for 3 years
Project Title: The role of VISTA in bowel cancer
While our immune system is sometimes about to attack and kill cancer cells, but in some cases it appears to not prevent tumours from growing. T cells form part of the immune system, and are able to recognise foreign molecules such as viruses, bacteria and even some cancer cells. The correct growth and development of these T cells is crucial to forming the full complement of white blood cells that recognises and destroys disease-causing pathogens. Incorrect T cell development leaves the body unprotected against infection and disease. Professor Noelle has discovered a new molecule, called VISTA, has a negative effect on T cell activation. High levels of VISTA can be found in areas surrounding tumours and it blocks the efficient anti-tumour immune response. His AICR grant will be used to study where VISTA is found in patients with bowel cancer and what effect it has on T cell function. It is hoped that blocking VISTA might be a promising target for cancer therapy.