Projects starting from January 2014 - June 2017
Grant Holder: Dr Maria Paola Paronetto
Institution: Fondazione Santa Lucia, Rome, Italy
Grant award: £108,090 for 3 years
Project title: Investigating the rare bone cancer, Ewing’s Sarcoma
Dr Maria Paola Paronetto is investigating a very rare type of cancer called Ewing’s Sarcoma (ES) which is commonly found in teenagers and young adults. It can develop anywhere in the body, although it most often starts in the bone. If caught early, before it has spread, 70% of patients survive for at least 5 years after diagnosis but that means 30% of patients don’t survive for 5 years after diagnosis. The survival rate also decreases the more advanced the disease is when diagnosed.
It is thought that ES may be related to rapid bone growth, hence why it is more common in growing teenagers, but its exact causes are still unclear and need further research. Some chromosomes are able to break away and fuse with other chromosomes, creating a potent cancer-causing gene that is thought to drive ES. Dr Paronetto is using her AICR grant to further investigate, at the molecular level, the proteins and pathways involved in the initiation of ES. She hopes to identify pathways or proteins that could be targeted by new therapeutic approaches in the future and help increase the survival rates for ES patients.
Grant Holder: Dr Giuseppina Caretti
Institution: University of Milan, Milan, Italy
Grant award: £134,790 for 3 years
Project title: Stopping muscle wasting in cancer patients
Many patients with cancer experience loss of weight and muscle wasting, a process known as cachexia. This process cannot be reversed by simply getting the patient to consume more calories and sadly, if the person has cachexia they are much less likely to survive. There are currently no effective treatments against muscle wasting in cancer and this is the focus of Dr Giuseppina Caretti’s AICR grant. She is focussing on a protein called myostatin which is present at high levels in cachexia. Dr Caretti hopes that by blocking myostatin and its effects, she can reverse muscle loss and increase survival time in mice. If successful, she hopes her work could later be tested in patients.
Grant Holder: Dr Steven Gamblin
Institution: National Institute for Medical Research, London, England
Grant award: £103,741 for 2 years
Project title: Understanding how a type of childhood leukaemia called mixed lineage leukaemia (MLL) begins.
Every cell in our body contains thousands of genes. Genes are like our blueprint - they determine everything that our cells do. Cancer is caused by changes to either the structure or activity of key genes that regulate how the cells operate, divide and die. One way that cells control this activity is to add specific chemical groups or 'tags' on to the genes, or the proteins that act as scaffolding for the genes, to ensure that only the correct genes are active. The addition of tags can lead to an increase or decrease in gene activity. This often happens incorrectly in cancers and the change in gene activity drives the cell to grow and divide in an uncontrolled manner, forming a tumour. It is incorrect tagging, and the resulting incorrect messages it causes, that leads to a type of childhood leukaemia called “mixed lineage leukaemia” or MLL. In MLL, several different proteins work together in a complex to control a protein called the MLL1 enzyme, which places these tags. The ultimate aim of Dr Gamblin's project is to produce a high resolution X-Ray structure of the MLL1 protein complex, so the researchers can see the exact shape and explain how it works. Dr Gamblin believes this work could help build the foundation for future drug development studies.
Grant Holder: Dr Jeroen van Bergen
Institution: Leiden University Medical Center, Leiden, Netherlands
Grant award: £210,546 for 3 years
Project title: Researching a therapy for the rare disease Enteropathy-Associated T-cell Lymphoma
Enteropathy-associated T-cell lymphoma (EATL) is a very rare type of T-cell lymphoma. It usually occurs in the small intestine, and is associated with celiac disease. It occurs in a small number of patients who do not respond to a gluten-free diet, the standard treatment for celiac disease, and who therefore suffer from chronic inflammation in their intestines. Patients having a massive increase in faulty, premalignant, white blood cells in their small intestine are at high risk for developing EATL. EATL is a fast-growing (aggressive) lymphoma and the future for these patients is not very good with an average five year survival of only 10-20%. New and better treatments are therefore urgently needed.
Together with his colleagues, Dr Jeroen van Bergen has discovered a small group of cells in the intestines that he believes could be key to the initiation of EATL. He is therefore using his grant to study how these begin to grow and divide rapidly, whilst avoiding death. Finally the team will look for chemicals or biological inhibitors that could stop these rogue cells from dividing and cause them to die. He hopes that his findings could provide important information to aid the treatment of EATL in the future.
Grant Holder: Dr Neta Erez
Institution: Tel Aviv University, Tel-Aviv, Israel
Grant award: £154,994 for 3 years
Project title: Investigating how skin cancer spreads to the brain.
Cutaneous melanoma is the most dangerous type of skin cancer and is responsible for the most skin cancer deaths. The reason for this is because cells often spread to distant organs, including the brain, where they form secondary tumours and stop the organs working correctly. With her AICR grant Dr Erez is investigating how special brain cells, called astrocytes, are involved in facilitating melanoma cells form a secondary tumour in the brain.
Grant Holder: Professor Andrew Giraud
Institution: Murdoch Childrens Research Institute, Melbourne, Australia
Grant award: £246,134 for 3 years
Project title: Investigating how stomach cancer begins and how to stop it.
Despite the progress being made in cancer research, stomach cancer is still one of the cancers with a low survival rate. In 2008 almost 990,000 people around the world were diagnosed with stomach cancer and 738,000 people died from the disease. Stomach cancer is strongly linked to prolonged inflammation of the lining of the stomach and changes in the bacteria found there. Professor Andrew Giraud is investigating the role a molecule called IL-11 plays in stomach cancer. He will be using mice models which mimic one of the early events preceding human stomach cancer caused by bacteria. A major focus of this work will not only be to understand how cancer begins, but to identify potential ways to stop the process. He hopes to take it further and find small molecules which could actually prevent stomach cancer occurring. If successful, and after extensive further research, his findings could potentially be used to try and treat people with stomach cancer.
Grant Holder: Professor Johanna Schleutker
Institution: University of Turku, Turku, Finland
Grant award: £184,554 for 3 years
Project title: Finding new genes involved in prostate cancer to help diagnose and treat patients
The cause of prostate cancer at the genetic level has so far been difficult to determine. Only a few ‘high risk’ genes and more common genetic mutations have been identified and they account for only a small number of cases. Professor Johanna Schleutker hopes to identify and characterise more genes involved in prostate cancer with her AICR grant. In particular, she hopes to find genes which predispose men to prostate cancer (meaning they have a higher chance of developing it than other people). She also hopes to find genes involved in the more aggressive type of the disease, which tends to affect younger men, as well as find genes that may influence how a man responds to prostate cancer treatments. In order to find these genes she will be using a combination of powerful new techniques, which can analyse vast amounts of data. Any genes discovered could be used to better diagnose prostate cancer, this is especially important for those men who have the more aggressive form of the disease and for whom early treatment is more urgent.
Grant Holder: Professor Fabienne Mackay
Institution: Monash University, Melbourne, Australia
Grant award: £192,070 for 3 years
Investigating and correcting immune system defects in Chronic Lymphocytic Leukaemia (CLL).
Chronic Lymphocytic Leukaemia (CLL) is the most common leukaemia in adults and currently has no cure. As leukaemia affects the white blood cells, which fight off infections, patients with CLL have a compromised immune system and suffer from recurrent infections, which can end up being fatal. It is therefore important to understand exactly how the immune system is compromised, in order to try to boost it in these people. Professor Mackay has identified two novel immune defects in patients with CLL, which she has replicated in a mouse model of the disease established in her laboratory. Together these defects lead to a suppressed immune system but via two distinct mechanisms. Professor Mackay believes these defects are key to disease progression. She is now using her AICR grant to prove that reversing these defects could help boost patient’s immune systems and anti-cancer defences. She will be using mouse models and human CLL tissue samples and hopes her findings could have a positive impact on CLL treatments in the future, benefitting many patients.
Grant Holder: Professor Giorgio Scita
Institution: IFOM The FIRC Institute of Molecular Oncology Foundation, Milan, Italy
Grant award: £186,036 for 3 years
Project title: Investigating how breast cancer cells become able to spread around the body
When tumours stay in one place they can be more easily treated with surgery and the patient has a higher chance of a good outcome. Cancer becomes more difficult to treat when the cancerous cells have started to spread away from the original tumour, invading blood vessels or the lymphatic system and migrating round the body where they start forming secondary tumours in other organs. It is often these secondary tumours that can kill the patient. If scientists can better understand how the cancer cells become physically able to break away from the original tumour and move, they could then find new and improved ways to stop it occurring. This is what Professor Giorgio Scita hopes to discover with his AICR grant. He is particularly focusing on a specific group of proteins and the role they play in the spread of breast cancer. If we could stop cancer tumours from spreading, the number of people surviving the disease will increase. This kind of research therefore has massive clinical implications for patients in the future.
Grant Holder: Dr Hans van der Vliet
Institution: VU University Medical Center, Amsterdam, Netherlands
Grant award: £190,414 for 3 years
Project title: Developing new treatments for multiple myeloma (MM).
Dr Hans van der Vliet is using his AICR grant to develop a new treatment for multiple myeloma (MM). MM develops from cells in the bone marrow called plasma cells. Normally, new plasma cells are produced to replace old, worn-out cells in an orderly, controlled way. However, in myeloma, the process gets out of control and large numbers of abnormal plasma cells (myeloma cells) are produced. These fill up the bone marrow and interfere with the production of normal white blood cells, red blood cells and platelets which causes many problems for the patient.
Dr van der Vliet is developing a new biological treatment against MM using parts of antibodies. These special antibodies act upon a protein called CD1d which is found at much higher levels on MM and triggering of CD1d has already been shown to kill MM cells in lab based tests. Another way to kill MM cells is by activating immune system cells designed to kill foreign bodies, with the catchy name gamma-delta T cells. Dr van der Vliet plans to combine both of these approaches to create an even more potent treatment which will first be tested in the lab and then in mice as no other methods can be used.
Dr Hans van der Vliet hopes that if successful, his new treatment could enter clinical trials in patients. He believes it could not only benefit patients with MM but potentially also people with chronic lymphocytic leukaemia (CLL), lymphomas, certain gliomas, breast, lung, prostate and bowel cancers which all have high levels of CD1d.
Grant Holder: Dr Kate Sutherland
Institution: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Grant award: £259,586 for 3 years
Project title: Identifying mutations that drive lung squamous cell carcinoma
Lung cancer is the leading cause of cancer deaths worldwide. Dr Kate Sutherland is using her AICR grant to study a type of lung cancer called squamous cell carcinoma (SqCC). In order to study the disease in a living system she will begin by developing a mouse model which mimics the human disease as accurately as possible. This will ensure that any findings she makes will be relevant to patients. Previous investigations looking at the genetic make-up of lung cancer tissue from patient samples have identified a range of mutations involved in lung cancer. However, it is unclear which are the initial mutations that cause the onset of cancer, and which occur later. It is important to identify these so new treatments can be developed to stop them initiating cancer. Dr Sutherland aims to find which genetic mutations cause the cancer to begin firstly using lab based techniques then validate her findings using her new mouse model system and tissue samples taken from lung cancer patients.
Grant Holder: Dr Meredith O’Keeffe
Institution: Burnet Institute, Melbourne, Australia
Grant award: £222,043 for 3 years
Project title: Investigating a syndrome called myelodysplasia and how it can turn into acute myeloid leukaemia (AML).
Dr Meredith O’Keeffe is studying a mouse model of myelodysplastic syndrome which has many features similar to the human syndrome, including progression to acute myeloid leukaemia (AML). AML is a type of cancer that affects white blood cells and bone marrow. AML usually develops quickly, over days or weeks and is the most common type of leukaemia in adults, usually in people over 65 years old.
Dr O’Keeffe has already found that these special mice have a much smaller number of dendritic cells in the bone marrow, which is also true of people with myelodysplasia. Dendritic cells are part of the immune system that helps our bodies recognise foreign bodies like bacteria or viruses. Dr O’Keeffe has also found that of those dendritic cells that remain, there are five distinct types. Her team are therefore investigating if the loss of these dendritic cells in the bone marrow actually exacerbates the disease and plays a role in the progression to AML. To do this she will be using both healthy mice and special mice that have the myelodysplastic syndrome. The team will also be confirming that their findings are relevant to humans by examining bone marrow samples from patients with myelodysplasia or AML and investigating the same five types of dendritic cells found in the mice. Dr O’Keeffe hopes to better understand the role of dendritic cells in the development of myelodysplasia and the transition to AML.
Grant Holder: Professor Hallgeir Rui
Institution: Thomas Jefferson University, Philadelphia, USA
Grant award: £183,925 for 3 years
Project title: New ways to model human breast cancer
The majority of newly diagnosed, aggressive breast cancers contain something called an oestrogen receptor on the surface of the breast cancer cells. This means that the presence of the female sex hormone, oestrogen, encourages the cells to grow. Many women can be successfully treated for their breast cancer but sadly it can come back, often elsewhere in the body, and this time is resistant to treatment. These tumours, known as secondary tumours or metastases, are typically the cause of death from cancer, not the original tumours. In order to study how this disease reoccurs and test treatments to kill these cancer cells, a new mouse model is vital. Professor Hallgeir Rui has been developing such an improved mouse model and is now using it to test new treatments for oestrogen receptor positive breast cancer cells which have spread to the lungs. Using mice to test new treatments is still a vital part of developing novel therapies and is a legal requirement for all new drugs licensed to give to patients.
Grant Holder: Professor Jos Jonkers
Institution: The Netherlands Cancer Institute, Amsterdam, Netherlands
Grant award: £199,200 for 3 years
Project title: Investigating drug resistance in triple-negative breast cancer patients
The overall survival rates for breast cancer are the best they have ever been, with more than three-quarters of UK women surviving for ten years or more after diagnosis. However, there are several different types of breast cancer and for one, called triple-negative breast cancer (TNBC), the survival rate is still not good. TNBC means the cancer cells do not possess the three common molecules on their cell surface, so TNBC patients cannot be treated with the drugs that are typically used for other breast cancer patients. A fraction of TNBC patients also have an inactive form of the molecule BRCA1 in the breast cancer cells, which causes problems but on the flip side, it does mean these cells can be killed by the drug olaparib. However, long-term treatment with olaparib leads to the cells becoming resistant, meaning they no longer die and the cancer can return. It is thought that a process called epithelial-to-mesenchymal transition (EMT) may play a role in this resistance, and this is the focus of Professor Jonkers' AICR grant. By better understanding how this drug resistance occurs, Professor Jonkers hopes his findings could help researchers identify new ways to potentially treat TNBC in the future.
Grant Holder: Professor Pierre van der Bruggen
Institution: de Duve Institut, Brussels, Belgium
Grant award: £185,208 for 3 years
Project title: Investigating how cunning cancer cells escape death by our immune system
Our immune system is made up of cells that have the ability to recognise foreign molecules – such as those found on bacteria, viruses and even some cancer cells. Once a foreign body, like a cancer cell, has been detected the immune system is usually able to attack and kill it. But cancer cells are cunning and have developed a wide range of ways to prevent the immune system from recognising or attacking them. Professor Pierre van der Bruggen is investigating one way cancer cells evade death by releasing molecules called galectins. He will be using samples taken from cancer patients and mice to study the role of galectins. He will also study the effect that blocking these molecules could potentially have on reducing tumour growth and ability to spread.
Grant Holder: Dr Flavio Curnis
Institution: Fondazione Centro San Raffaele, Milan, Italy
Grant award: £ 177,096 for 3 years
Project title: Improving the delivery of cancer drugs to tumours
Dr Curnis is using his AICR grant to develop new ways to deliver cancer drugs to tumours using something called nanodrugs. He has previously contributed to the development of a drug called NGR-TNF, which is in phase II and phase III clinical trials in humans. That means it has already passed many levels of checking and is in the final stages of assessment in humans. NGR-TNF works due to something called a peptide, similar to a postcode, which ensures the drug (or letter) goes to the right place, in this case, blood vessels in the tumour.
Dr Curnis has now developed several new codes and will produce new TNF-based nanodrugs loaded with these new codes and to look at how good they are at getting to a tumour and killing it, whilst having no other toxic effects on the body. He will do this by testing the nanodrugs alone and alongside standard chemotherapy to see if it makes an even more potent treatment. This work has the potential to improve treatments for many cancer patients in the future.
Grant Holder: Professor Michael Olson
Institution: Beatson Institute for Cancer Research, Glasgow, Scotland
Grant award: £190,547 for 3 years
Project title: How can we stop cancers from spreading?
One of the things that make tumours so dangerous is the ability of certain cancer cells to invade into surrounding tissues and organs, and then spread throughout the body. The resulting secondary tumours can cause organs to fail and has been directly linked with 90% of cancer deaths. Professor Michael Olson believes he has identified a molecule, called MRCK, that plays a major role in allowing certain cancer cells to spread. If MRCK can be turned off or blocked, this could potentially stop this process. Professor Olson is using his AICR grant to better understand the role of MRCK in cancer spread and, as all cancers are different, which cancer types would be more susceptible to death when treated with drugs to turn off MRCK.
Grant Holder: Dr Christian Frezza
Institution: Hutchison/MRC Research Centre, Cambridge, England
Grant award: £191,002 for 3 years
Project title: Investigating a cancer syndrome called Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC).
Cancer occurs when something goes wrong to allow certain cells in our bodies to grow and divide in a rapid and uncontrolled manner, forming a tumour. In order to grow so quickly, the cells need more energy than normal. They are able to increase their own metabolism to generate this energy as the cells have internal power houses. For a certain type of aggressive kidney cancer, called Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), genetic mutations in a protein called Fumarate Hydratase cause a fault in the cell's power house machinery. This means the cells cannot make energy in the normal way. It is not yet understood how these cancer cells are able to cope with the demands for high energy levels without a properly functioning powerhouse. This is therefore the focus of Dr Christian Frezza's AICR grant, to understand how the cells adapt. He will be using computer systems and mouse models to carry out his investigations. If scientists could identify the cell’s Achilles heel and understand how they compensate, they could then make drugs to block this ability and kill the cancer cells.
Grant Holder: Dr Clemens Cabernard
Institution: University of Basel, Basel, Switzerland
Grant award: £199,743 for 3 years
Project title: Understanding how cell division can go wrong and lead to cancer
All of the information that our cells require is carried in long, sausage-shaped structures called chromosomes. When a cell divides to produce two new cells, it firstly has to copy all of its chromosomes and then give one complete set to each new cell. This process is very carefully controlled because if something goes wrong and one cell gets an incomplete or increased set of chromosomes it can make the cell malfunction - and in some cases can lead to it becoming cancerous. The location at which the cells start to divide in two plays a key role in this process. A molecule called GTPase RhoA plays a vital role in determining where on the original cell it will divide to form the new cells and this is what Dr Clemens Cabernard is investigating. This kind of basic research is very important as there is still much we don't know about how cancer occurs in the first place. Understanding the fundamental principles like how cell division goes wrong can make finding ways to stop cancer occurring much easier in the future.
Grant Holder: Professor Noel Lowndes
Institution: National University of Ireland Galway, Galway, Ireland
Grant award: £204,340 for 3 years
Project title: Understanding the role of the protein ATR in copying DNA
For cells to grown and divide, all the DNA needs to be precisely and accurately copied in order to pass a full and correct version to each of the new daughter cells when the divide. In order to do this there are many complex copying and quality control systems in place inside the cell. Defects in these systems can lead to ‘replication stress’, which is known to contribute to cancer development. A key regulator protein in all of this is ATR, which responds to replicative stress. Professor Noel Lowndes is using his AICR grant to investigate the roles of ATR, and a related protein called H2ax, in controlling DNA replication in both the absence and presence of replication stress. This type of project is important for scientists to fully understand what happens in normal, healthy cells which, in future, may also help them understand some of the many things that go wrong in cancer cells.
Grant Holder: Dr Federica Benvenuti
Institution: International Centre for Genetic Engineering and Biotechnology (ICGEB), Triste, Italy
Grant award: £80,630 for 2 years
Project title: Understanding how the immune system can encourage tumours to grow
Cancerous tumours do many sneaky things in order to survive and keep growing. Normally, immune system cells can attack and kill cancer cells. However, some in tumours, special immune system cells can be tricked into stopping the immune system from killing cancer cells and can actually switch and encourage the growth of tumours. This leads to a much poorer outcome for patients. How this occurs is not fully understood and this is the focus of Dr Federica Benvenuti’s AICR grant. In particular she is focussing on a protein called VAMP-3 which she believes plays a key role. By having a better understanding of how the cells switch from anti-cancer to encouraging it, Dr Benvenuti hopes her findings could aid the development of better treatments for patients in the future.
Grant Holder: Professor Ton Schumacher
Institution: The Netherlands Cancer Institute, Amsterdam, Netherlands
Grant award: £200,000 for 3 years
Project title: Investigating a type of immune system cell called Tregs and their role in the tumour mass
A special kind of immune system cell, called intratumoral regulatory T cells (Tregs), is often found in a tumour mass. In some cancer types, where these Tregs are found, they are associated with a poorer clinical outcome for patients. This is because Tregs are able to suppress the immune system to stop it attacking the tumour. It is therefore assumed that interfering with these cells could make the tumours more sensitive to cancer treatments, and mean a more successful outcome for the patient. There is still much unknown about Tregs however and their role and influence inside the tumour. It is important to better understand Tregs so scientists can then predict how they may react and the impact this may have, when the tumours are treated with cancer therapies. This is therefore the focus of Professor Ton Schumacher’s AICR grant. In order to carry out the work he will be using melanoma skin cancer samples from patients, the most dangerous form of skin cancer.
Grant Holder: Professor Seamus J Martin
Institution: Trinity College Dublin, Dublin, Ireland
Grant award: £129,404 for 3 years
Project title: Understanding the conflicting processes of cancer cell survival and death
If cells become damaged, they can activate a suicide mechanism called apoptosis. Several cancer drugs work by trying to take advantage of this and forcing the damaged cancer cells to self-destruct. A molecule called Fas has previously been identified as a trigger for apoptosis and drugs have been designed to turn Fas on. However, there had been reports of Fas having other counteractive roles in cell movement and cell growth. Fas has been found at high levels in cancers of the kidney and ovaries suggesting that Fas may play a pro-cancer role as these cells often fail to undergo apoptosis. To agree with this, recent studies have found that cancer cell growth, tumour progression and invasion into surrounding tissues can all be impaired by turning off Fas. Therefore, instead of triggering the cancer cells to die, the cells can actually benefit from having high levels of Fas. With his AICR grant Professor Martin is aiming to investigate these pro-cancer roles of Fas in certain cancer. He expects that his findings could be real game changers which will alter everyone’s current perspectives of Fas and could have serious implications for research on drugs that try to turn on Fas in the hope of triggering apoptosis.
Grant Holder: Professor Marco Foiani
Institution: IFOM The FIRC Institute of Molecular Oncology Foundation, Milan, Italy
Grant award: £169,656 for 3 years
Project title: Investigating additional roles of the key DNA-damage protein ATR
Professor Foiani is using his AICR grant to study a protein called ATR. ATR is well known to be involved in repairing damaged DNA to prevent cells becoming cancerous but Professor Foiani has recently found it plays another role in response to external cell stress. This stress could be sudden changes in the concentration of molecules surrounding the cell, causing a rapid movement of water across the cell membrane into or out of the cell, or some sort of physical stimulation. Under these conditions, ATR gets turned on and moves from its normal location to the nuclear membranes which encircles the nucleus, the 'brain' of the cell. Professor Foiani believes ATR plays a role in a mechanical response to cell membrane stress that helps pass messages into the nucleus through the nuclear membrane. This allows the cells to then react to the external stress. By understanding the role of ATR better, it could help researchers develop better cancer treatments in the future.
Grant Holder: Professor Stéphane Thore
Institution: University of Geneva, Geneva, Switzerland
Grant award: £209,084 for 3 years
Project title: How do hormones drive the growth of some cancers?
Many cancers, including breast, prostate, bowel and pancreatic, are driven to grow and invade nearby tissues by hormones, chemicals produced in the body. Hormones do this by interfering with communication pathways inside the cells, leading to changes in key genes which control how our cells grow, divide and die. The exact molecules and genes the hormones interact with and the effects this has are not fully understood and so with his AICR grant Professor Thore aims to investigate this. He hopes that his findings will reveal several ways that hormone-driven cancers could be targeted by new cancer drugs.