Projects starting from 1st January 2012 to 31st December 2014
Grant Holder: Dr Claudia Wellbrock
Institution: University of Manchester, England
Grant Award: £174,036 for 3 years
Project Title: Searching for new treatments for skin cancer
Dr Wellbrock is using her AICR grant to investigate new treatments for melanoma skin cancer, the most dangerous type of skin cancer. Melanoma is usually resistant to many of the cancer treatments. Last year a new drug was shown to be highly effective in killing these type of tumours but sadly many patients became resistant to the treatment very quickly, meaning the drug no longer worked but it is still unclear why or how. Dr Wellbrock has discovered a new way this drug resistance may have occurred and is now searching for drugs that could turn this resistance mechanism off. She will test the drugs in a zebrafish model of melanoma which will also allow her to test other treatments at the same time. In the future, new drugs, like those being researched by Dr Wellbrock, could be given alongside other treatments to help kill the melanoma cells and prevent drug resistance.
Grant Holder: Professor David A Gillespie
Institution: Beatson Institute for Cancer Research, Scotland
Grant Award: £165,590 for 3 years
Project Title: Investigating the control checkpoints within our cells
Cancer can be caused by damage to the DNA inside our cells. This damage can be due to many things such as UV from sunlight or the DNA can become altered or damaged as it is being copied when the cells are growing and dividing to form new cells. All cells have mechanisms to detect and repair this DNA damage, to prevent them becoming cancerous. These detection and repair mechanisms can sometimes become altered or faulty which allows the DNA damage to remain, allowing the cells to become cancerous and tumours to develop. Professor Gillespie is using his AICR grant to study a molecule involved in these mechanisms called Chk1. In particular he will be investigating which other molecules Chk1 interacts with and how they control whether Chk1 is turned on or off. Professor Gillespie hopes that his findings will help researchers understand how damaged DNA can be allowed to remain and its role in cancer progression.
Grant Holder: Professor Stella C Knight
Institution: Imperial College London, England
Grant Award: £136,104 for 2 years
Project Title: Understanding the link between obesity, the immune system and bowel cancer
Bowel cancer is one of the most common types of cancer and around 1.24 million new cases were diagnosed around the world in 2008.
There is an established link between obesity, the immune system and bowel cancer. Recent evidence has suggested that the molecule leptin, produced by fat cells, could be involved in this link between obesity and bowel cancer as its levels are higher in obese people and it is reported to encourage the growth of bowel cancer. The activity of the immune system is controlled by specific immune system cells called dendritic cells which determine whether or not the immune system responds to cancer cells. These dendritic cells also make leptin and they can carry certain types of fat around the body.
Professor Knight is using her AICR grant to study a pre-cancerous condition called familial adenomatous polyposis (FAP) which goes on to develop into bowel cancer. It is not currently known what role leptin plays in FAP and what type of fat that the dendritic cells carry. She will therefore be investigating how obesity, leptin, fat and dendritic cells are all involved in the progression from FAP to bowel cancer. Professor Knight hopes that her results could help with the development of a therapy that could potentially prevent bowel cancer by increasing the immune system's ability to fend off the disease before the onset of cancer.
Grant Holder: Assistant Professor Emily Bernstein
Institution: Mount Sinai School of Medicine, New York, ESA
Grant Award: £207,353 for 3 years
Project Title: Understanding the causes of melanoma skin cancer
Genetic information is like our cellular blueprint - it determines how ourcells function. Cancer can be caused by changes to either the structure oractivity of key genes that regulate how cells operate, divide and die. Oneway that cells control the activity of genes is to add specific chemical groups or 'tags' on to the genes themselves or the proteins which act as scaffolding for the genes to ensure proper regulation. The addition of these tags can lead to an increase or decrease in gene activity. This often happens incorrectly in cancers and changes in gene activity may drive the cell to grow and divide in an uncontrolled manner, forming a tumour. Assistant Professor Emily Bernstein is using her AICR grant to study the role of tagging in malignant melanoma, the most dangerous type of skin cancer.
Grant Holder: Professor Wilhelm Krek
Institution: ETH Zurich, Zurich, Switzerland
Grant Award: £175,554 for 2 years
Project Title: Investigating liver cancer
Primary liver cancer is quite rare. In total, about 3,600 cases are diagnosed in the UK each year and it is more common in men than in women. However, for those that do get it the outlook is poor because by the time someone has symptoms and goes to their doctor, the disease is very often in the advanced stages. Only about 1 out of 10 people (10%) are diagnosed in the early stages of this disease when surgery can help. AICR have recently awarded a grant to Professor Wilhelm Krek to study how liver cancer begins.
Cells have a complex internal system of genes and proteins which control everything they do. These genes and proteins are organised into pathways in which the first activates the second and that activates the third, and so on, passing the activation signal down the pathway. Several signalling pathways are involved in controlling how cells grow and divide and can become significantly altered in cancer cells. One of these, known as the mTOR pathway, is known to be turned on in liver cancer and has been linked to poor survival for patients.One of the molecules at the end of the mTOR signalling pathway is URI. URI is often found at high levels in liver cancer and correlates with increased cell growth and poor patient survival. It is thought that it is involved in switching off cell suicide messages and promoting cell survival in cancer cells. With his AICR grant Professor Krek therefore intends to investigate how it does this.
Grant Holder: Professor Julia Newton-Bishop
Institution: University of Leeds, England
Grant Award: £189,118 for 2 years
Project Title: Investigating the genetic causes of malignant melanoma skin cancer
There are two main types of skin cancer; the more common and less dangerous non-malignant melanoma and the less common but more dangerous malignant melanoma.Professor Newton Bishop and her team have collected one of the largest malignant melanoma sample and data sets in the world. They have recruited over 1,900 patients and are following their progress for at least 8 years. Such large collections are needed to understand such a complex disease.
Advanced malignant melanomas have always been difficult to treat. There has been recent progress for some types of malignant melanoma; drug therapies are producing encouraging results in tumours that have genetic alterations in the gene called BRAF. However, in most patients these drugs gradually lose their effectiveness and much remains to be understood as to why. Also, for other types of malignant melanoma tumour the main genetic causes remain unknown.
One of the problems when studying malignant melanoma is that the tumours are very small, meaning little material to use for research. Professor Newton Bishop’s team have developed ways of producing large amounts of genetic information from tiny samples of the tumours stored by hospitals as part of clinical care. Using these samples, Professor Newton Bishop aims to investigate the genetic types of malignant melanoma as well as identifying genetic alterations that may indicate whether or not the cancer is likely to come back. She will also be investigating whether any such genetic alterations could be turned off using drugs.
Grant Holder: Dr Angeliki Malliri
Institution: University of Manchester, England
Grant Award: £181,395 for 3 years
Project Title: Investigating how cancers can spread around the body
One of the main things that make tumours so dangerous is their ability to invade into surrounding tissues and organs then spread throughout the body, known as metastasis. Individual cancer cells push their way through the tissue and are then carried in the blood stream and can form new tumours in other parts of the body, known as secondary tumours or metastases. One protein involved in this process is called Rac1. Dr Malliri has recently found that Rac1 is able to interact with another type of protein called an E3-ubiquitin ligase. E3-ubiquitin ligases work by sticking ubiquitin molecules onto proteins. This often flags up to the cell that the ubiquitin coated proteins should be destroyed. Dr Malliri is now using her AICR grant to study the E3-ubiquitin ligase’s ability to stick ubiquitin onto Rac1 and what role this plays in allowing tumours to spread.
Grant Holder: Professor David J MacEwan
Institution: University of East Anglia, Norwich, England
Grant Award: £193,106 for 3 years
Project Title: Understanding how Acute Myeloid Leukaemia cells avoid dying
Acute Myeloid Leukaemia (AML) is rare and is most common in people over 65 years old. Current treatments are mainly only suitable for younger and fitter patients, meaning there is a need for better treatments for many patients. Professor MacEwan and his team have recently identified a molecule called Nrf2 which is able to help the cell avoid dying, even when treated with chemotherapy drugs but it is still not clear exactly how it can do this. One theory is that acute myeloid leukaemia cells have high levels of Nrf2. Professor MacEwan is now using his AICR grant and samples from patients to fully investigate how Nrf2 is able to cause this protective effect on the acute myeloid leukaemia cells. He hopes that his results could aid the development of better treatments for acute myeloid leukaemia patients in the future.
Grant Holder: Dr Jacqueline D Shields
Institution: Hutchison/MRC Research Centre, Cambridge, England
Grant Award: £161,364 for 3 years
Project Title: How do tumours avoid attack by our immune system?
It has long been suspected that our immune system has the potential to attack and kill cancer cells. However, at least in some cases, it appears not to actually prevent tumours from growing as they have a variety of ways to prevent the immune system from recognising or attacking them. One way the tumour does this is by accumulating non-cancer cells to create something known as a ‘tumour stroma network’, although it is still unclear how this protects the tumour from the immune system and encourages it to grow. There are also lymphatic vessels (tubes) whose main role is to drain fluids and other molecules from leaky blood vessels and provide an escape route for cancer cells. Interestingly, these lymphatic vessels also provide a direct connection between the immune system and the tumour, making it more confusing how the tumours can grow and thrive. Dr Shields is using her AICR grant to try to determine how the tumours manage to evade attack by the immune system. In particular she is focussing on the role of the lymphatic system and the tumour stroma network.
Grant Holder: Professor Claudio Sette
Institution: Fondazione Santa Lucia, Rome, Italy
Grant Award: £139,050 for 3 years
Project Title: Investigating how prostate cancer starts and spreads
Prostate cancer is the most common cancer in men in the UK and worldwide, around 899,000 men were diagnosed with prostate cancer in 2008. Despite the high number of men getting this disease there is still much to be known about how it starts and spread. AICR has therefore recently awarded a grant to Professor Sette to investigate some of the molecules involved in allowing prostate cancer to start and spread.
Every cell in our body contains thousands of genes that are in control of all that happens within the cell. Cancer is caused by changes to either the structure or activity of specific, key genes that control how the cells grow, divide and survive. These gene changes cause the cells to multiply in a rapid and uncontrolled manner, forming a tumour.
A new way that cells control the activity of their genes involving molecules called long non coding (lnc) RNAs has recently been discovered. lnc RNAs have been shown to be involved in many human diseases, including prostate cancer.
Professor Sette has previously shown that a protein called Sam 68 is also involved in controlling gene activity in prostate cancer cells and is present at high levels in these cells. Sam68 can control the activity of genes in several different ways, either directly or by effecting lnc RNAs which then control the gene’s activity. With his new AICR grant he is aiming to understand exactly how Sam68 works with other molecules in the cell, including lnc RNAs, and what effects it has on prostate cancer cells. A better understanding of Sam68’s role in cancer cells may help with the development of new prostate cancer therapies in the future.
Grant Holder: Dr Oskar Fernandez-Capetillo
Institution: Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Grant Award: £115,500 for 3 years
Project Title: How can we kill cancer cells but not healthy cells?
One of the reasons that many cancer treatments have such severe side effects is that they kill healthy cells rather than just the cancerous ones. Researchers are therefore working hard to find things that make the cancer cells unique, then trying to make drugs that selectively kill them and leave the others unharmed. One of the ways that cancer cells are unique is that they often have large amounts of DNA that gets damaged when it is copied and which is not repaired as it is in healthy cells. Dr Fernandez-Capetillo is using his AICR grant to investigate this type of damaged DNA to see if it could be targeted for cancer treatment.
Grant Holder: Dr Luke Gaughan
Institution: University of Newcastle upon Tyne, England
Grant Award: £182,736 for 3 years
Project Title: Understanding why some women become resistant to breast cancer treatment
Female breast cancer incidence rates in Great Britain have increased by more than 50% over the last twenty-five years. In 2008 almost 47,700 women and 340 men were diagnosed with breast cancer. Happily, breast cancer survival rates have been improving over the last 40 years but while it still claims the lives of around 11,500 women and 80 men in the UK each year, more research is needed.
The growth of many breast cancers is dependent on the hormone estrogen. An effective treatment for these breast cancers is tamoxifen, which works by blocking estrogen from attaching to its ‘docking station’ called the estrogen receptor. However, some breast cancers do not die and are resistant to this treatment or they can develop resistance over time this is what AICR have awarded a grant to Dr Luke Gaughan to investigate.
One reason for the resistance could be other molecules incorrectly controlling the activity of the estrogen receptor. Dr Gaughan has previously identified two molecules, called JMJD1A and JMJD2B, which are somehow able to do this. With his new AICR grant he is now trying to determine how JMJD1A and JMJD2B are involved and how they work with each other to turn on the estrogen receptor. He will be carrying out his work in a range of different types of breast cancer cells to see if JMJD1A and JMJD2B work the same way in all of these cells.
Ultimately, these results could provide evidence that turning off JMJD1A and JMJD2B may be a potential new way to treat breast cancer. This would mean drugs to turn off these two molecules could then be sought.
Grant Holder: Dr Richard Callaghan
Institution: Australian National University, Australia
Grant Award: £163,928 for 3 years
Project Title: Understanding how people become resistant to chemotherapy.
Despite the success of chemotherapy in treating cancer, a large number of patients become resistant to the drugs. This means that the cells stop dying and the cancer can continue growing or return. One way the cancer cells are able to adapt is by making ‘pumps’ that sit in the membrane surrounding the cell and enable the chemotherapy drugs to pumped out, ensuring the cancer cell does not die. The production of lots of these pumps is associated with poor patient prognosis and lowered rates of the cancer entering remission. An obvious option is to find a way to ‘plug’ these pumps but sadly this is not as easy as it sounds. One of these pumps is called P-gp and its exact shape has recently been determined. With this new knowledge Dr Callaghan has identified a specific site on the P-gp pump that could possibly be filled with a drug to stop it from working. He is now using his AICR grant to investigate this site by carrying out an in depth analysis which could help provide information on the shape and type of drug which may stick to this specific site.
Grant Holder: Dr Alison Woollard
Institution: University of Oxford
Grant Award: £185,930 for 3 years
Project Title: Using worms to help us understand cancer
Researchers often use tiny worms called C. elegans to understand how cells grow, divide and die. Many of the genes and proteins found in these worm cells are also present in human cells. Since worms are less complicated, grow faster and are easier to study than humans they enable scientists to see changes more quickly and do experiments that could not be done on humans. Dr Woollard has recently found two ‘anti-cancer’ genes called unc-62 and ceh-20 that are present in the worm cells and are very similar to genes that are also found in human cells. She is now investigating how these two genes are turned on and how they control the way cells grow and divide, including their role in cancer.
Grant Holder: Dr Maria Pia Protti
Institution: Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy
Grant Award: £185,992 for 3 years
Project Title: Investigating the role of the immune system and inflammation in pancreatic cancer
Worldwide, around 279,000 people were diagnosed with pancreatic cancer in 2008. Sadly this type of cancer has a poor prognosis. By the time someone has symptoms, goes to their doctor and is diagnosed, the disease is very often quite advanced. Dr Maria Pia Protti is using her AICR grant to investigate whether the immune system has a role in inducing or increasing inflammation in pancreatic cancer. To carry out this work she will be using human samples from pancreatic cancer patients.
Grant Holder: Professor Paul Clarke
Institution: University of Dundee, Scotland
Grant Award: £164,089 for 3 years
Project Title: Investigating how cancer cells multiply and avoid dying
Healthy cells grow and then divide to form two new cells in a highly organised and tightly controlled manner. Cancer can occur when the cells become able to grow and divide more rapidly in an uncontrolled manner, leading to the development of tumours. Cancer cells are also often resistant to cell death and are able to divide even when they are damaged. These differences can be an advantage, however, if the mechanisms that prevent the normal death of damaged cells can be overcome, because cancer cells can be killed selectively whilst leaving healthy cells unharmed.
Professor Clarke is using his AICR grant to study a molecule called Mcl-1 which is found at high levels in many cancer cells. Mcl-1 has an important role in preventing damaged cells from dying, including during the cell division process. If cancer cells are treated with drugs like Taxol, then Mcl-1 is often destroyed and the cells can be killed. However, other molecules work against this mechanism and can prevent Mcl-1 being destroyed, leading to resistance to the drug. Therefore, if researchers can find a way to turn off these opposing molecules, this could allow Mcl-1 to be removed more effectively and ensure the cancer cells die in response to drugs like Taxol.
Grant Holder: Dr Sílvia Beà Bobet
Institution: Fundacio Clinic per la Recerca Biomedica, Barcelona, Spain
Grant Award: £183,892 for 3 years
Project Title: Investigating Mantle Cell Lymphoma
Mantle cell lymphoma is a rare type of Non-Hodgkin Lymphoma (cancer of the lymphatic system - part of our immune system) and its causes are still unknown. It is mostly found in middle aged to older individuals (60-65 years) and is more common in men than women. The median survival for mantle cell lymphoma is only 3-5 years and sadly the vast majority of patients cannot be cured. However, there are a small number of patients who have a stable form of the disease and do not need treatment for long periods of time. With her AICR grant Dr Beà is analysing samples from mantle cell lymphoma patients (aggressive and the more stable forms) to identify which alterations are responsible for the disease and to understand the genetic reasons for this difference in how patients respond to the disease.
Grant Holder: Dr Pipsa I Saharinen
Institution: University of Helsinki, Finland
Grant Award: £123,533 for 2.5 years
Project Title: Investigating the growth of blood vessels towards tumours
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. New drugs that can prevent tumours from doing this are therefore being sought by scientists as a way to treat cancer patients.
One molecule involved in the growth of blood vessels is Ang2. Using animal models and human patients it has already been shown that turning off Ang2 can reduce the growth of tumours, including advanced tumours which often remain unaffected by current cancer drugs designed to block tumour blood vessel growth.
While turning off Ang2 seems to hold promise as a new way to treat tumours, little is known about what Ang2 actually does in the cell. Dr Pipsa Saharinen is therefore using her AICR grant to investigate the role of Ang2 and what effects may be caused if it is turned off in cells to stop blood vessel growth. She will also try to discover what other molecules Ang2 works with. This information will be extremely important if drugs that switch off Ang2 are developed further as a way to prevent the growth and spread of cancer.
Grant Holder: Professor D. Gareth R Evans
Institution: University of Manchester, England
Grant Award: £55,099 for 2 years
Project Title: Researching tumours of the nervous system
Every cell in our body contains thousands of genes. Cancer is caused by changes to either the structure or activity of key genes that regulate how the cells operate, divide and die. These changes cause the cells to multiply in a rapid and uncontrolled manner, forming a tumour. Professor Gareth Evans is using his AICR grant to investigate two of the most common types of nervous system tumour, meningioma and schwannoma which occur in the inherited conditions neurofibromatosis type 2 and schwannomatosis. For some tumours the genes which are altered have been identified, for example the NF2 and the SMARCB1 genes, but for many tumours the genetic alterations causing the disease are still unknown and there can often be several genes altered before the tumours develop. The main aim of Professor Evans' project is therefore to try to find previously unidentified genes that become altered and which allow the development and growth of these nervous system tumours. For any altered genes identified he will also try to find ways to block the effect of the alteration using drugs.
Grant Holder: Dr Pawel Swietach
Institution: University of Oxford, England
Grant Award: £191,403 for 3 years
Project Title: Investigating the regulation of pH in cancer cells
In order to remain healthy, it is important that cells maintain a constant internal pH. Cells are constantly defending their pH balance against chemicals like acid produced by the body, for example, as a result of making energy and breathing. The cells have to pump out the excess acid or alkali which is then taken away by the nearby blood supply. Cancer cells have an even harder struggle to maintain their pH levels as they produce more acid and have a poorer blood supply. The surrounding connective tissue cells also play a role in pH maintenance of the cancer cells and this is what Drs Swietach and Hulikova are using their AICR grant to investigate. A greater understanding of the role of these connective tissue cells could aid with the development of improved cancer treatments in the future.
Grant Holder: Dr Daniela Palacios
Institution: Fondazione Telethon, Rome, Italy
Grant Award: £254,109 for 3 years
Project Title: Investigating the causes of Rhabdomyosarcoma
Rhabdomyosarcomas are a group of highly malignant tumours that account for over half of the soft tissue sarcomas in children. Sadly, current therapies, consisting of surgery combined with chemotherapy, are not sufficient in the most aggressive forms of the tumours, meaning better treatments are needed.
Rhabdomyosarcomas originate from muscle stem cells. Muscle stem cells are special cells that can change into mature muscle cells through a process called differentiation. However, in Rhabdomyosarcomas something goes wrong, allowing the cells to grow out of control and escape the differentiation program. Dr Palacios is using her AICR grant to investigate the role of a protein called p38 in the development of rhabdomyosarcoma. In normal muscle cells p38 must be switched on in order to form muscle. However, in some rhabdomyosarcomas the protein is not turned on, and this is linked to uncontrolled cell division and tumour formation. Thanks to support from AICR, Dr Palacios will investigate what happens if she forces p38 to be turned on in rhabdomyosarcoma cells. In particular she will look at how it alters the genes in the cancer cells in order to stop them from dividing and allowing their differentiation into healthy muscle cells.
Dr Palacios will start by using rhabdomyosarcoma cells grown in the laboratory before confirming her findings using samples taken from children with the disease. She hopes her research will lead to a new way of grouping these tumours based on the types of treatments that work best. She also hopes the findings could help with the design of new treatments for rhabdomyosarcoma.
Grant Holder: Dr Axel Behrens
Institution: London Research Institute
Grant Award: £120,942 for 2 years
Project Title: Investigating the molecules involved in bowel cancer
Worldwide, bowel cancer is the third most common cancer type, an estimated 1.24 million people were diagnosed with the disease in 2008. Incidences of bowel cancer are highest in the Western world. But with westernisation of the diet in several Asian countries new cases are increasing. Age is the most likely cause of bowel cancer, and what we eat has plays a large part in the development of bowel cancer, but we do not yet fully understand the mechanisms that are involved in causing the disease. Dr Behrens is using his AICR grant to investigate the communication pathways inside our cells that can lead to bowel cancer. In particular he is focussing on a molecule called PRMT1 and whether switching it off with drugs could help in the treatment of bowel cancer.
Grant Holder: Professor Roberto Chiarle
Institution: University of Turin, Italy
Grant Award: £170,900 for 3 years
Project Title: Investigating how and why our chromosomes can break
All of the information that our cells require is carried in coded instructions in our DNA. The DNA is packaged into long, sausage-shaped structures called chromosomes. Sometimes parts of one chromosome can break off and join on to another chromosome. This can be very bad as it can encourage pro-cancer genes to be turned on in an inappropriate manner, allowing the onset or progression of cancer. Professor Chiarle is using his AICR grant to study how and when these breaks can occur and their role in cancer.