Grants starting October 2007 and ending October 2010
Grant Holder: Dr Hanudatta Atreya
Institution: Indian Institute of Science, Bangalore, India
Grant Award: £54,025 for 3 years
Project Title: A new way to control how cancer cells grow
The blood contains a number of molecules, called growth factors, that encourage cells to grow and multiply. Two of the most powerful of these are called IGF-1 and IGF-2. However, the blood also contains proteins that stick to these IGF growth factors called IGF Binding Proteins or IGFBPs. When the growth factors are bound to IGFBPs they stop them from working. Therefore the amount cells grow is controlled by the levels of these IGFBPs - the more IGFBP, the less IGF available for cell growth. Since cancer is caused by cells growing and dividing in a rapid and uncontrolled way, Dr Atreya wants to find out if the IGFBPs can be developed as a potential treatment for cancer. He is studying how the IGFBPs bind to the IGFs, to determine if the IGFBPs can be altered to make them stick tighter and be more effective at slowing down the growth of the cancer cells.
Grant Holder: Dr Jean-Christophe Marine
Institution: University of Ghent, Belgium
Grant Award: £140,789 for 3 years
Project Title: Understanding communication pathways in childhood eye cancer cells
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 of these signalling pathways are involved in controlling how cells grow and divide and can become significantly altered in cancer cells. The p53 pathway has been found to be altered in half of all human cancers, causing the cells to multiply rapidly and out of control. Dr Marine is studying a type of childhood eye cancer called retinoblastoma. He has discovered that in retinoblastoma the changes to the p53 pathway are caused by increased levels of a protein called Mdmx. He is now going to develop a new strain of mouse which has increased levels of Mdmx in the retina cells in their eyes, in order to study retinoblastoma. These mice will be used to study the way this cancer develops and to test out new drugs as potential treatments for the cancer.
Grant Holder: Professor Aymen Al-Shamkhani
Institution: University of Southampton , England
Grant Award: £180,552 for 3 years
Project Title: Helping our immune system to fight cancer
Our immune system is made up of cells that can recognise foreign molecules – such as those found on the surface of bacteria, viruses and even some cancer cells. Once a foreign cell has been detected the immune system is able to attack and kill it. Experiments have suggested that, without the immune system, some anti-cancer drug treatments are significantly less effective. The immune system may therefore play an important role in finishing off cancer cells after the drugs have attacked them. But cancer cells have a wide range of ways to prevent the immune system from recognising or attacking them. One molecule involved in preventing an anti-cancer immune response is phosphatidyl serine, which is present on the surface of dying cancer cells. It does this by tricking the immune system into thinking that this is part of the normal process of tissue re-generation and therefore switches off the ability of the immune system to kill cancer cells. Prof Al-Shamkhani is making molecules that bind to the phosphatidyl serine (on the surface of cells) and prevent it from working. This will enable the immune system to be activated in order to attack both living and dying cancer cells more effectively.
Grant Holder: Dr Elizabeth Patton
Institution: University of Edinburgh, Scotland
Grant Award: £188,578 for 3 years
Project Title: How do harmless moles turn into dangerous skin melanomas?
Melanoma - the most dangerous form of skin cancer - can develop after over-exposure to UV light from the sun or sunbeds. We do not fully understand how this occurs so understanding the role of UV light in mole and melanoma development is a key question in melanoma research. In order to how find out more Dr Patton is using a simple model system called a zebrafish. Like humans, zebrafish have the pigment producing cells found in moles that can change into melanoma. Dr Patton has developed a strain of zebrafish that carries an alteration in the genes most frequently found in human moles and melanoma. This genetic alteration causes the same skin changes in the fish and leads to the development of moles and melanoma. Using this model system Dr Patton is identifying which other genes are involved in the development of moles and melanoma, and investigating exactly what part each of the genes play.
Grant Holder: Dr Dong-Yan Jin
Institution: University of Hong Kong
Grant Award: £145,021 for 3 years
Project Title: Investigating how errors in the way cells divide cause leukaemia
Our genes, are packaged into 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 daughter cell. This process is very carefully controlled because giving an incomplete or too large a set of chromosomes can make a daughter cell function incorrectly. This is what happens in many leukaemias where the white blood cells have too many chromosomes or two unrelated chromosomes have joined or fused together. Dr Jin is investigating a rare type of leukaemia which is partly caused by the HTLV-1 virus. HTLV-1 contains a gene called Tax which can affect another protein in the white blood cells called TAX1BP2. TAX1BP2 is involved in copying chromosomes and when Tax affects the TAX1BP2 protein, it upsets the normal mechanism for separating the chromosomes when the cell divides. This results in the two new cells having additional or fused chromosomes. With a grant from AICR, Dr Jin is studying how Tax causes this malfunction in dividing blood cells, what else Tax interacts with and how this contributes to leukaemia.
Grant Holder: Dr Jeremy Blaydes
Institution: University of Southampton, England
Grant Award: £150,777
Project Title: Understanding how cells grow and die
Cancer can be caused by damage to the DNA which makes up our genes. This damage is produced by many things such as UV from sunlight or chemicals in cigarette smoke. All cells have mechanisms to prevent them becoming cancerous by either repairing this damage or making the damaged cells kill themselves. A protein called p53 has an extremely important role in controlling how cells grow and die. Normally, p53 appears to prevent cells from becoming cancerous but it has been found to be damaged or absent in half of all human cancers. Another protein, called HDMX, controls the amount of p53 in cells and Dr Blaydes has discovered a new mechanism that controls the amount of HDMX in cells, and therefore the amount of p53. He is now investigating how this mechanism works in normal and cancer cells.
Grant Holder: Professor Laura Machesky
Institution: University of Glasgow, Scotland
Grant Award: £156,657
Project Title: How cancer cell movement leads to cancer spread
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. Individual cancer cells squeeze between the normal cells nearby and push their way through the tissue. This ability to move and spread is controlled by information in our genes, but we do not yet know which genes. Professor Machesky is using a new genetic technique to switch off every gene known to be involved in cell movement, one at a time, and then test the cells ability to invade the surrounding tissue in a special model system. This will help identify exactly which genes control the ability of cancer cells to spread.
Grant Holder: Dr Marielle C Haks
Institution: Leiden University, Netherlands
Grant Holder: £180,700 for 3 years
Project Title: Hijacking our immune system to make it fight cancer
Our immune system contains a variety of white blood cells, all with different jobs. Some, known as CTLs have the ability to recognise molecules on the surface of foreign bodies - such as bacteria, virus-infected cells and even some cancer cells. Once a foreign body has been detected the CTLs are able to attack and kill it. Researchers are trying to exploit this natural event to develop anti-cancer treatments but cancer cells have a variety of ways to prevent the immune system from recognising or attacking them. The CTLs have certain specialized molecules on their surface. Scientists recently discovered that increasing the activity of one called 4-1BB, dramatically boosts their killing power. However, increasing the activity of 4-1BB on CTLs occasionally lessens their attack but we do not know how or why. Because the outcome of increasing 4-1BB activity is still unpredictable, this strategy is not yet suitable as an anti-cancer treatment. Dr Haks is therefore studying the mechanisms inside the CTLs that are activated by 4-1BB. She has already identified the genes that are turned on when 4-1BB is activated on CTLs to boost their killing capacity and is now going to examine what each of the genes does. Her aim is to use these genes to increase the CTLs killing power without the risk of ‘accidentally’ lessening their attack.
Grant Holder: Professor Chris J Hutchison
Institution: Durham University, England
Grant Award: £195,551 for 3 years
Project Title: How to put cancer cells into a coma
Healthy cells grow and divide in a tightly controlled manner by a process known as the cell cycle. Cancer occurs when the cells become able to multiply in a rapid and uncontrolled manner, leading to the formation of a tumour. Many anti-cancer drugs work by blocking different sections of the cell cycle and preventing them from dividing. Professor Hutchison is investigating how two proteins called lamin A/C and LAP2 alpha are involved in regulating the cell cycle. When these proteins are missing or inactive the cells cannot divide and enter a coma-like state, suggesting that these proteins might be good targets for new anti-cancer drugs. Professor Hutchison is therefore using his AICR grant to investigate how blocking the activity of these proteins in cancer cells causes them to stop dividing.
Grant Holder: Dr David Meek
Institution: University of Dundee, Scotland
Grant Award: £85,833 for 3 years
Project Title: How do cells control their growth?
Every cell contains thousands of genes to help make proteins. These proteins then carry out a variety of important roles within the cells. Many of these genes and proteins are altered in cancer cells and therefore operate quite differently, causing the cells to grow and divide rapidly in an uncontrolled manner, forming a tumour. A protein called p53 has an extremely important role in controlling how cells grow, divide and die. Normally, p53 appears to prevent cells from becoming cancerous but it has been found to be damaged or absent in half of all human cancers. The amount of p53 in cells is regulated by another protein called MDM2. Dr Meek has now found that a third protein, called FKBP25, regulates the amount of MDM2 and therefore indirectly regulates the amount of p53. With his AICR grant he is now investigating how FKBP25 does this and what happens if FKBP25 is absent or inactive in cells.
Grant Holder: Dr Reuben Tooze
Institution: University of Leeds, England
Grant Award: £163,255 for 3 years
Project Title: Determining which molecules cause lymphoma
Our immune system contains white blood cells which recognise foreign cells and attack them. Lymphoma is caused when some of the white blood cells (lymphocytes) in the immune system start growing and dividing in a rapid and uncontrolled manner. With a grant from AICR Dr Tooze is investigating what goes wrong to allow this to happen. The two key molecules involved are BLIMP1 and IRF4. BLIMP1 has been found to have anti-cancer properties in the cells and is known as a tumour suppressor. Normally, BLIMP1 regulates the activity of IRF4 by making it less active but in lymphoma cells where BLIMP1 is absent IRF4 is found to be active and present at high levels. Dr Tooze aims to find out if this increased level of IRF4 activity is involved in causing lymphomas by studying other genes that BLIMP1 and IRF4 interact with. This will give him a much better understanding of how these key molecular systems work and what goes wrong to cause lymphoma.
Grant Holder: Dr Olga Sinilnikova
Institution: CRNS, Lyon, France
Grant Award: £103,226 for 3 years
Project Title: Identifying which genes increase a woman’s risk of breast or ovarian cancer
Back in the 1990’s scientists discovered the BRCA1 and BRCA2 genes that, when damaged or altered, cause a high risk of breast cancer. Although we can now test women for damage to these genes, we are still unable to clearly identify which women are most at risk of developing breast or ovarian cancer. This is because in some cases women with similar damage in the two BRCA genes still have different levels of risk. This suggested that there are additional genes involved that can alter a person’s level of risk. Using her AICR grant Dr Sinilnikova is investigating whether eight genes that code for key molecules in a system called the NMD pathway may be involved in causing this variation in cancer risk. She is analysing the genes of 2000 women with damaged BRCA genes to determine whether differences in their NMD genes alters their risk of breast and ovarian cancer. It is hoped that in the future Dr Sinilnikova’s work may help make it possible to accurately determine how great a risk some women have of getting these cancers.
Grant Holder: Professor Paola Defilippi
Institution: University of Turin, Italy
Grant Award: £112,500 for 3 years
Project Title: Dissecting the communication pathways in breast cancer
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. These pathways are very complex, with many cross-overs and branches. Several of these signalling pathways are involved in controlling how cells grow and divide and can become significantly altered in cancer cells, causing cells to multiply in a rapid and uncontrolled manner. Professor Defilippi is studying a protein called p130Cas which is involved at the cross over point of several of these pathways. Breast cancers with high levels of p130Cas are usually aggressive and more likely to be resistant to treatments like tamoxifen. Using a mouse strain that have high levels of p130Cas in their breast cells, Professor Defilippi is studying the role p130Cas plays in normal breast tissue and breast cancers, as well as its role in the various signalling pathways in the cell.
Grant Holder: Dr Daniela Barila
Institution: University of Roma, Italy
Grant Award: £52,818 for 2 years
Project Title: How do cancer cells escape death?
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. These pathways are very complex, with many cross-overs and branches. Several of these signalling pathways are involved in controlling how cells grow and divide and can become significantly altered in cancer cells, causing the cells to multiply in a rapid and uncontrolled manner. Dr Barilà recently discovered a new interaction/crossover between several pathways that regulate the balance between cell growth and cell death. The Src pathway, containing the protein Src, is involved in controlling cell growth and movement while caspases are the main proteins involved in the cell suicide pathways. Both the Src and cell suicide pathways are known to be altered in cancers. Dr Barilà discovered that the Src protein could modify the caspase-8 protein in one of the cell suicide pathways, impairing cell death and probably encouraging the cells to move. This modification could therefore contribute to cancer development and progression. With her grant from AICR she is investigating how this modification works in normal cells and whether it holds any clues as to how some cancers develop.
Grant Holder: Dr Pietro Pichierra
Institution: ISS, Rome, Italy
Grant Award: £127,671 for 3 years
Project Title: How do cells proofread your DNA?
When a cell divides to produce two new cells, it firstly has to copy all of its DNA and then give a complete set to each of the daughter cells. This process is very carefully controlled because giving a faulty or incomplete set can make the new cell malfunction – and in some cases it can lead to it becoming cancerous. Any mistakes in the DNA copying causes the process to stall, the rescue mechanism then corrects the mistake and allows the copying to restart. Dr Pichierri has discovered that if the main rescue mechanism has been lost in the cell then an alternate, less precise rescue mechanism takes over, which allows some errors to creep into the copying process. With a grant from AICR he is analysing this alternate mechanism to find out how it works and what happens if it is switched off.
Grant Holder: Dr Claude Sardet
Institution: CRNS, Montpellier, France
Grant Award: £111,903 for 3 years
Project Title: What goes wrong to cause skin cancer?
Proteins carry out most of the jobs within cells and they control processes such as how the cells grow, divide and die. Dr Sardet has been studying a protein called E4F1. Little is known about E4F1 except that it is involved in cell growth and survival. E4F1 works closely with another protein called p53, which has been found to be damaged or absent in half of all human cancers. Recently Dr Sardet has found that E4F1 also interacts with another protein called p63, a member of the same group of proteins as p53. p63 is involved in cancer development in skin and in the tissue that lines internal organs. Dr Sardet discovered that if the E4F1 protein is missing in skin cells, there is a massive overgrowth of these cells, similar to skin cancer. This suggests that E4F1 has anti-cancer properties. With a grant from AICR, Dr Sardet is now analysing the roles that E4F1 and p63 play in normal skin cells and how they prevent skin from becoming cancerous in order to understand what goes wrong in cancer.
Grant Holder: Professor Alan Rickinson
Institution: University of Birmingham, England
Grant Award: £177,373 for 3 years
Project Title: How does the Epstein-Barr virus cause cancer?
A high percentage of the world's population are infected with the Epstein-Barr virus and carry the virus for life without it ever causing them harm. However, this same virus is linked to a number of different types of cancer. These include particular cancers of a white blood cell called a B lymphocyte, and this is the main cell type the virus infects in the body. The virus is also found in important cancers of another cell type, called an epithelial cell. The virus is more often found in the epithelial cells which line the nasal cavity and, in rare cases, the lining of the stomach. Little is known about how the virus gets into epithelial cells to cause these cancers, the problem being that it has been very difficult to make the virus infect these cells in the laboratory. Professor Rickinson and his team in Birmingham have now discovered a way to do this, by attaching the virus to the surface of its usual target cell, the B lymphocyte, and using that as a vehicle to transfer the virus from one cell type to the other. With AICR support, the team is using this technique to investigate exactly how the transfer process occurs, which cell molecules are involved and what effect the virus has on “transfer-infected” cells.
Grant Holder: Professor Eamonn Maher
Institution: University of Birmingham, England
Grant Award: £110,659 for 3 years
Project Title: Understanding the cause of childhood kidney cancer
Perlman syndrome is an inherited condition in which children are born with severe abnormalities. About half of those affected develop Wilms tumour, a common childhood cancer of the kidneys. Professor Maher is trying to find the exact gene that causes Perlman syndrome. He has already identified the approximate location of the gene and so with a grant from AICR he is now analysing all the genes in this area from samples of children with Perlman syndrome to find out which gene is damaged and causing the syndrome. Once the exact gene is identified he will study the role of the normal, undamaged version of the gene and the role of the damaged version in causing Wilms tumour.
Grant Holder: Dr Jens Siveke
Institution: Technical University of Munich, Germany
Grant Award: £128,518 for 3 years
Project Title: Investigating pancreatic cancer using a model system
Pancreatic cancer rarely produces any early symptoms and is therefore often diagnosed too late for any effective treatment. Research into this disease has been hampered by a lack of good animal models to study how the disease starts and progresses. Dr Siveke has now developed a mouse model with certain genes missing which allows tumours to develop. He will now use this mouse model to identify changes in the systems regulating the initiation and progression of pancreatic cancer.
Grant Holder: Dr Patrick Humbert
Institution: Peter Macallum Cancer Centre, Melbourne, Australia
Grant Award: £134,640 for 3 years
Project Title: Understanding how breast cancer cells spread
Most of the cells in human tissues exist in layers, with an ‘up’ side and a ‘down’ side and they have systems to tell the difference between up and down. However, when they become cancerous, cells grow and spread in all directions, meaning that they have lost their sense of up and down. Early experiments in fruit flies identified the genes that control this sense of up and down in cells and it is thought these may be the same in humans. There is growing evidence to suggest that one of these genes, called Scribble, is absent or damaged in human cancers of the breast lining. Therefore Dr Humbert is using his AICR grant to examine what role Scribble has in cells. He aims to determine how the loss of Scribble affects the control mechanisms inside cancer cells and allows the breast tumours to spread.
Grant Holder: Dr Dimitris Kontoyiannis
Institution: Fleming Institute, Greece
Grant Award: £89,443 for 3 years
Project Title: Understanding what causes bowel cancer
Every cell carries a complete set of genetic blueprints called genes that are made of DNA. Genes are coded instructions to make proteins which carry out activities within the cell. In order to make proteins the genes must become active. The activated genes then produce an RNA molecule, similar to DNA, which is used as a template to make a protein. However, there are some proteins, called RBPs, which stick to RNA molecules and can influence how efficient they are at making proteins. These RBPs are known to stick to and control some of the RNA molecules involved in cancer and the response of cancer cells to inflammation. If the regulation is lost then the cells can grown and divide in an uncontrolled manner, leading to a tumour. Dr Kontoyiannis is using his AICR grant to investigate the role of RBPs in bowel cancer.
Grant Holder: Dr Onno Kranenberg
Institution: University of Utrecht, Netherlands
Grant Award: £120,295 for 3 years
Project Title: Investigating how cancer cells can spread into nearby tissue.
Every cell in our body contains thousands of genes. Cancer is caused by changes to either the structure or activity of certain genes that regulate how the cells operate, divide and die. If the regulation is lost then the cells can grow and divide in an uncontrolled manner, leading to a tumour. Dr Kranenberg has been studying one such gene called KrasD12. He discovered that blocking the activity of this gene prevents cancer cells from spreading. Stopping cancer cells from spreading to surrounding tissue is one of the biggest challenges for doctors as successful treatment is much harder once it has spread. Dr Kranenberg has identified 62 other genes that are activated by KrasD12 and with his AICR grant he wants to find out which of these also give the cells their ability to invade other tissue and spread around the body. To do this he is using a technique called RNAi to inactivate each of these genes, one at a time, then test the cells for their ability to invade and spread.
Grant Holder: Dr Juan Valcárcel
Institution: Centre for Genomic Regulation, Barcelona, Spain
Grant Award: £147,273 for 3 years
Project Title: How do cells become cancerous?
Every cell contains a complete set of genetic blueprints called genes. Cancer is caused by changes to the shape or activity of certain genes that regulate how the cells operate, divide and die. If this regulation is lost the cells can grow in a rapid and uncontrolled manner, causing a tumour. This is because the genes are coded instructions to make proteins, which carry out activities within the cell. In order to make proteins the genes must become active. The activated genes then produce an RNA molecule, similar to DNA, which is used as a template to make a protein. However, before that can happen, the RNA molecule has to be pruned and shortened by removing ‘junk’ sections in the middle, a process called RNA splicing. Dr Valcárcel is investigating how RNA splicing is controlled for 3 proteins involved in making cells become cancerous.
Grant Holder: Professor Guido Kroemer
Institution: Gustave Roussey, Villejuif, France
Grant Award: £101,939 for 3 years
Project Title: How our immune system helps anti-cancer drugs fight the disease
Our immune system, which is made up of white blood cells, can recognise and attack any cells displaying foreign molecules. Foreign molecules are ones not normally found in the body – such as those found on the surface of bacteria and viruses. When cancers are treated with drugs, the dying cells also display foreign molecules on their surface and there is evidence that, in some cases, the immune system attacks them. Experiments have suggested that, without the immune system, some anti-cancer drug treatments are significantly less effective. The immune system may therefore play an important role in finishing off cancer cells after the drugs have attacked them. Professor Kroemer has discovered that the ability to attack dying tumour cells depends on a molecule called TLR4 on the surface of white blood cells. He is now investigating which anti-cancer drug treatments are helped by the immune system and exactly what mechanisms the TLR4 molecule uses to make white blood cells attack the dying tumour cells.
Grant Holder: Dr Tuna Mutis
Institution: University of Utrecht, Netherlands
Grant Award: £155,579 for 3 years
Project Title: How to make the immune system fight cancer cells but not healthy cells
Our immune system, which is made up of white blood cells, can recognise and attack any cells carrying ‘foreign’ molecules – ie molecules not normally found in the body. Since many tumour cells carry strange molecules on their surface, sometimes, the immune system can attack and kill these also. One situation where this occurs is when leukaemia patients are given bone marrow stem cell transplants. Once the bone marrow stem cells are transplanted they develop into new white blood cells. Unfortunately, since the transplanted cells are from another person, they recognise all of the recipient’s cells as foreign and start to attack all of their body tissues. Normally, the recipient patient is given drugs to suppress this attack on their tissues, but these drugs also suppress the attack on the cancer cells. There is evidence to suggest that these two actions of the immune system – attacking normal tissues and attacking cancer cells – are different and it may be possible to switch one off and the other on. Dr Mutis is analysing the cells that control the immune system to find out if some of them can stop the attack on the normal tissues, without affecting the fight against the cancer cells.
Grant Holder: Dr Jos Jonkers
Institution: Netherlands Cancer Institute, Amsterdam
Grant Award: £234,448 for 3 years
Project Title: How does breast cancer start?
Every cell in our body contains thousands of genes. Cancer is caused by changes to either the shape or activity of certain 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. Often several different genes have to be changed for a cell to become fully cancerous. For example, damage to a gene called E-cadherin in a type of breast cancer called lobular breast cancer makes it much more aggressive and likely to spread around the body. However, we do not yet know which other genes have to be damaged to initiate this type of cancer. Dr Jonkers will be using a strain of mouse without the E-Cadherin gene to search for the other genes responsible for causing lobular breast cancer. Using a sophisticated genetic technique, he will identify which changes in which genes are, together with E-cadherin loss, responsible for this type of cancer.
Grant Holder: Dr Pascal Meier
Institution: Institute of Cancer Research, London, England
Grant Award: £179,041 for 3 years
Project Title: Using fruit flies to investigate how cancer cells escape cell death
Cancer is caused by damage or alterations to certain genes that control the way cells grow, divide and die. Normal cells are programmed to respond to high levels of gene damage by killing themselves using a suicide mechanism. In many cancer cells this suicide mechanism has been deactivated meaning the cells are invincible and fail to die. Dr Meier is using fruit flies as a model system to study how the cell suicide mechanism operates and how it is deactivated in cancer. With his AICR grant he is focusing on a protein called Dark that is known to be part of this mechanism. This project aims to identify the mechanism through which the killer protein Dark is activated. He is using molecular and genetic tools to identify proteins that interact with Dark and activate it following damage to the cell.
Grant Holder: Professor Anne Dejean
Institution: Institute Pasteur, Paris
Grant Award: £153,000 for 3 years
Project Title: How do cells control their activities?
All of the processes and functions that take place inside cells are carried out by proteins. One way that cells control the activity of the proteins is to modify them by adding on or taking away specific chemical groups to increase or decrease their activity. Professor Dejean is studying one particular type of chemical modification – the attachment of another small protein called SUMO. In particular, she is studying the proteins that repair damage to genes, many of which only work when they have SUMO attached. This is particularly important as cancer can be caused by damage to certain genes that control how the cells operate, divide and die. This damage causes the cells to grow and divide in a rapid and uncontrolled manner, forming a tumour. The repair genes are vital to make sure any damage to the genes is fixed and thereby protect the cells from becoming cancerous. Professor Dejean is aiming to understand the role of SUMO in normal cells in order to determine what goes wrong in cancer cells.
Grant Holder: Dr David Bates
Institution: University of Bristol
Grant Award: £163,143 for 3 years
Project Title: Why does the cancer drug Avastin work for some cancers but not others?
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. To do this they release hormone-like substances that encourage blood vessels to grow towards them and create a new blood supply. The main substance the tumours release is called VEGF. Recently a new anti-cancer drug called Avastin was developed that prevents VEGF from working, therefore stopping tumours from getting a blood supply. However, Avastin only appears to work on some tumours and not others. Professor Bates has discovered that there are several types of VEGF, some of which prevent the growth of new blood vessels (inhibitory VEGF) but not all of them. Different tumours produce varying amounts of the different types of VEGF. Therefore Professor Bates is investigating whether the variable response to Avastin is due to the variation in the amount of the different VEGFs that the tumours produce. This would mean that in the future the drug could be given only to patients with the type of tumour which would respond well to Avastin.
Grant Holder: Dr Pierre Hainaut
Institution: IARC, Lyon, France
Grant Holder: £125,300 for 3 years
Project Title: Predicting how a breast tumour will respond to treatment
Currently, it is difficult to predict how well a breast cancer tumour will respond to treatment. It is therefore important to find new molecule ‘markers’ to help predict how a breast tumour will react to drugs and to aid the development of more effective drugs. Every cell in our body contains thousands of genes that regulate how the cells operate, divide and die. Some genes have anti-cancer properties, known as tumour supressors. One such gene is TP53, known to be altered or damaged in many breast cancer tumours which respond poorly to cancer treatments. With his AICR grant Dr Hainaut is studying alterations in TP53 and how TP53 is involved in several of the main communication pathways inside cells, known to be deregulated in cancer cells. He hopes that in the future his findings can be used to predict how well breast cancer patients may respond to treatment.
Grant Holder: Dr John Martens
Institution: Erasmus University, Rotterdam
Grant Award: £131,428 for 3 years
Project Title: Understanding breast cancer prognosis and therapy response.
Cancer is caused by changes to either the structure or activity of certain genes that control how cells grow, divide and survive. Scientists have recently discovered a new way that cells control the activity of their genes involving molecules called microRNAs. There is evidence that some of these micro-RNAs play a role in cancer, including breast cancer. Dr Martens is investigating whether the differences in the micro-RNAs involved in patients determine whether breast cancers are mild or aggressive and how they will respond well to treatment. He is analysing the micro-RNAs in many hundreds of human breast cancers and correlating them with the outcome of the patient each case.
Grant Holder: Professor Andrew Cato
Institution: Karlsruhre Research Centre, Germany
Grant Award: £131,428 for 3 years
Project Title: Investigating new ways to treat advanced prostate cancer
Prostate cancer cells need the male sex hormone androgen to grow and multiply. The main drug treatments for this type of cancer work by blocking this effect of androgens. However, advanced prostate cancers no longer require androgens and the drugs do not work on them. Using his AICR grant Professor Cato is trying to find new ways to kill the advanced prostate cancer cells. He is using small molecules to try to stop these cancer cells growing and hopes that his results may also help treat other types of cancer.
Grant Holder: Dr David Waugh
Institution: Queens University Belfast, Northern Ireland
Grant Award: £166,828 for 3 years
Project Title: Understanding how prostate cancer spreads to the bone
When prostate cancers break away from the initial tumour, they almost always spread to the bone, which causes severe pain and fractures. Bone is a complex tissue in which the hard, mineral structure is constantly being broken down and simultaneously rebuilt. Prostate cancers do not seem to spread to bone where this process of breakdown and rebuilding has stopped. Dr Waugh has found that spreading prostate cancer cells produce a hormone-like substance called IL-8, which appears to affect the process of bone breakdown and rebuilding. Using his AICR grant he is investigating what role IL-8 plays in this process and how it affects the spread of prostate cancer. He aims to find out if blocking the breakdown and rebuilding of bone may be a way to prevent cancer from spreading there.
Grant Holder: Professor Craig Robson
Institution: University of Newcastle
Grant Award: £166,768 for 3 years
Project Title: Understanding prostate cancer at the molecular level
Prostate cancer cells normally only grow and divide in the presence of the male sex hormone androgen, which activates a protein called the androgen receptor. The main drug treatments for prostate cancer work by blocking the effect of androgens on the androgen receptor. However, in advanced prostate cancer the cells become able to multiply without androgens, meaning the drugs no longer work. Professor Robson has found that the androgen receptor in these advanced cancer cells is modified, meaning it can become active without the need for androgens. Until recently it was thought that only one type of chemical modification, called phosphorylation, was important. However, there is growing evidence that an alternative modification, called methylation, is also involved. Professor Robson is going to analyse the role that histone methylation plays in altering the androgen receptor and the effect this has on the growth and multiplication of prostate cancer cells.