Projects starting from May/June 2010 and ending May/June 2013
Grant Holder: Professor Ian Hickson
Institution: University of Oxford, UK (England)
Grant Award: £188,669 for 3 years
Project Title: Investigating the role of the PICH molecule in bowel cancer
Basic and part Bowel cancer
All of the information that our cells require is carried in code in the DNA which makes up our genes. The genes themselves are packaged into long, sausage-shaped structures called chromosomes. When a cell divides to produce two new cells, it first has to copy all of its chromosomes and then give one complete set to each of the two new cells. This process is very carefully controlled because an altered, incomplete or too large a set of chromosomes can make a cell malfunction – and in some cases it can lead to the cell becoming cancerous. Cancer can also be caused by damage to the DNA. All cells have mechanisms to repair this damage, to prevent them becoming cancerous, but these repair mechanisms can sometimes become faulty which can allow the DNA damage to remain, causing the cells to become cancerous. There is evidence that two molecules called PICH and BLM are involved in repairing damaged DNA and ensuring that new cells get the correct number of chromosomes. Professor Hickson has found that PICH is missing in some bowel cancers, suggesting that PICH may have anti-cancer properties. He is using his AICR grant to study how these two molecules interact with each other and what goes wrong in cancer cells.
Grant Holder: Professor Justin Stebbing
Institution: Imperial College, Healthcare NHS Trust, UK (England)
Grant Award: £184,074 for 3 years
Project Title: Understanding breast cancer
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. Nearly one thousand microRNAs have been identified and each one appears to be able to influence the activity of numerous genes in laboratory experiments. Some of these microRNAs appear to play a role in cancer but many of the genes the microRNAs control, and how they work, is not yet clear. Professor Stebbing is using his AICR grant to understand and establish the mechanisms of how microRNA families, specifically those that target the oestrogen receptor and other breast cancer processes, are activated.
Grant Holder: Professor Thomas J Gonda
Institution: University of Queensland, Australia
Grant Award: £202,058 for 3 years
Project Title: How can we improve breast cancer treatments?
Some breast cancer cells only grow in the presence of the female sex hormone oestrogen and are therefore known as oestrogen receptor positive breast cancers. Previously Professor Gonda showed that the MYB protein is needed for the growth of these cells and allows them to keep multiplying even in the presence of DIAs, molecules which usually either turn the breast cancer cells into different, non-growing cell types or kill them. One way MYB does this is by blocking mechanisms which cause the cells to undergo cell suicide, but it is not clear how. Professor Gonda is using his AICR grant to investigate what other genes and proteins MYB controls. Using breast cancer cells and model systems which mimic breast cancers, he will then test drugs which block the activity of MYB or of any proteins he identifies to see if that increases cell suicide. Professor Gonda hopes that using drugs that block MYB or cause cell suicide together with DIAs will help kill off breast cancer cells more effectively.
Grant Holder: Dr Michelle M Hill
Institution: University of Queensland, Australia
Grant Award: £174,742 for 3 years
Project Title: What is the link between obesity, cholesterol and prostate cancer?
Currently, there is a known link between prostate cancer, obesity and high cholesterol. How these conditions are linked remains unclear. A cell is covered by a cell membrane; this separates the inside of the cell from its external environment. Cholesterol is a component of this cell membrane that helps to organize the membrane into regions that are important for communication of the cell with the outside. One molecule that is controlled by cholesterol is called caveolin-1, and this molecule may play a role in aggressive prostate cancers. Dr Hill is using her AICR grant to investigate how caveolin-1 and high cholesterol are involved in prostate cancer. One theory is that the caveolin-1 molecule becomes altered in prostate cancer which causes changes in the way the cell membrane functions. These changes increase the ability of the prostate cancer cells to invade surrounding tissues and spread around the body, forming secondary tumours. Dr Hill and her team will test this theory using prostate cancer cells with or without caveolin-1 to mimic aggressive and non-aggressive prostate cancers, and study how these cells respond to changes in cholesterol in their environment. As the number of obese people increases and the population continues to eat a high cholesterol diet, a better understanding of how cholesterol and caveolin-1 contribute to prostate cancer is vital. Dr Hill’s team will use this system to find new molecules that could be used in diagnosis and to enable scientists to design and develop better treatments for prostate cancer in the future.
Grant Holder: Dr Roberto Gherzi
Institution: Istituto Nazionale per la Ricerca sul Cancro, Italy
Grant Award: £265,322 for 3 years
Project Title: Investigating the role of the KSRP protein
Dr Gherzi is studying a protein called KSRP which plays a role in how our cells grow and divide to produce new cells, but the exact details are unclear. It is important to understand how healthy cells are regulated so we can understand what goes wrong to allow the uncontrolled cell growth and division which can lead to the development of tumours. Using model systems, cells and tissue samples from mice Dr Gherzi is looking at the effect of removing KSRP. Some early results show that mice lacking KSRP develop stomach cancer more quickly than those with KSRP and he wants to confirm this. Dr Gherzi also wants to understand what role KSRP plays within cells, how it interacts with other proteins and molecules and the effects that any modifications on KSRP may cause.
Grant Holder: Dr Rui G Martinho
Institution: Insituto Gulbenkian de Ciencia, Portugal
Grant Award: £120,681 for 3 years
Project Title: Using fruit flies to understand how cancer begins
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. One way that cells control the activity of genes is to add specific chemical groups or ‘tags’ on to the genes or on to the proteins which act as scaffolding to ensure the genes can work correctly. This tagging often happens incorrectly in cancers and the changes can drive the cell to grow and divide in an uncontrolled manner, forming a tumour. Dr Martinho is using fruit flies to study a type of tagging called N-terminal acetylation in order to understand its role in the growth and division of healthy cells and in the development of cancer. Researchers often use flies to understand how cell growth and division is controlled. Most of the genes and proteins found in fly cells are also present in human cells and since fly cells are less complicated and grow quickly, they are easier to study and enable scientists to see changes more quickly.
Grant Holder: Dr Rudi W Hendriks
Institution: Erasmus University, Rotterdam, Netherlands
Grant Award: £200,000 for 3 years
Project Title: Understanding how chronic lymphocytic leukaemia begins
Dr Hendriks is using his AICR grant to investigate chronic lymphocytic leukaemia (CLL) which is the most common leukaemia in the western world. In particular, he is looking at the role of the immune system, which fights infections, and how it may contribute to the development of leukaemia. Using a special strain of mouse he will identify important genes which are involved in allowing or enabling leukaemia to start when the immune system is activated in different ways. Most of the genes in mice cells are very similar to those in human cells and Dr Hendriks therefore hopes to identify genes responsible for the development and growth of chronic lymphocytic leukaemia in humans.
Grant Holder: Dr Torsten Krude
Institution: University of Cambridge, UK (England)
Grant Award: £114,170 for 3 years
Project Title: Investigating the location of Y RNA molecules inside the cell
When a cell divides to produce two new cells, it first has to copy or replicate all of its DNA and then give one complete copy to each of the two new cells. It was previously shown that molecules called Y RNA’s are involved in the process of DNA replication but it is not yet fully understood how this works. Dr Krude is investigating whether the location of Y RNA’s inside the cells may play a role in this activity. He is using his AICR grant to look at where in the cell the Y RNA molecules are found, if they interact with other molecules and how this could be involved in regulating DNA replication.
Grant Holder: Dr Wim Vermeulen
Institution: Erasmus Medical Center, Netherlands
Grant Award: £205,633 for 3 years
Project Title: Understanding how our cells respond to UV from sunlight
Cancer can be caused by damage to the DNA inside our cells, for example from UV from sunlight. Healthy cells have mechanisms which can detect and repair this damage to prevent diseases such as cancer from occurring. But these repair mechanisms can sometimes become faulty which allows the DNA damage to remain causing the cells to become cancerous and tumours to develop. Dr Vermeulen is studying one particular DNA repair mechanism, called Nucleotide Excision Repair or NER for short. In particular he wants to find out how the NER mechanism is triggered into action following exposure to UV light and which proteins are involved.
Grant Holder: Professor Lambertus Kiemeney
Institution: Radboud University Nijmegen Medical Center, Netherlands
Grant Award: £196,954 for 3 years
Project Title: Improving prostate cancer screening
Prostate cancer is the most frequently diagnosed cancer among men in the UK. It is estimated that 5-10% of cases are due to faulty genes passed on from our parents. Faults in two particular genes called BRCA1 and BRCA2, appear to cause a higher risk of prostate cancer and men with faulty BRCA2 genes also tend to develop the more aggressive forms of the disease which have lower survival rates. The prostate specific antigen (PSA) test helps detect prostate cancer but it is not perfect. Although the test has helped decrease the number of deaths from prostate cancer by around 20% it also leads to over-detection and over-treatment for many men who would have continued living a normal and full life, usually when they have mild forms of this cancer. However, men at a higher risk of developing prostate cancer, and particularly the more aggressive form, for example those with faulty BRCA1 or BRCA2 genes, may be more likely to benefit from PSA screening. Professor Kiemeney is conducting a study looking at the use of the PSA test for men with different faults in their BRCA genes along with a second screening test for prostate cancer which detects the molecule PCA3 in urine. Professor Kiemeney will then evaluate the use of the PCA3 marker in screening high-risk families with the hope that if it is successful, it could be added to the screening programme for men with a higher risk of developing the disease.
Grant Holder: Dr Frederik J Hes
Institution: Leiden University Medical Center, Netherlands
Grant Award: £200,000 for 2 years
Project Title: Investigating bowel cancer risk
Our genes hold the instructions that tell our cells what to do – when to grow, divide and die. Most of our genes are identical from person to person but there are small variations within them which make us unique. In recent years scientists have been finding that small variations in certain genes also seem to increase or decrease a person’s risk of certain cancers. Some people are born with a higher risk of bowel cancer due to inheriting a faulty gene or genes from one or both of their parents or a combination of gene variants that each contribute to a small increase in risk. With a grant from AICR Dr Hes is studying patients with adenomas, small growths which are often present before bowel cancer develops, to try and identify new genes that increase the risk of developing bowel cancer. As researchers like Dr Hes unravel more about our genes and the cancer risk they cause, it will become possible to predict an individual’s risk of cancer more accurately. This can help identify those people who may need to take extra preventative steps or medication to reduce their chance of getting cancer.
Grant Holder: Dr Owen Sansom,
Institution: Beatson Institute for Cancer Research, UK (Scotland)
Grant Award: £209,451 for 3 years
Project Title: Finding new ways to stop bowel cancer
The way that healthy cells grow, divide and die is normally tightly regulated by our genes. Cancer is caused by changes to certain genes which cause the cells to keep growing and dividing in an uncontrolled manner, forming a tumour. In most cases of bowel cancer, a gene called APC is altered, becoming responsible for causing the tumours. In healthy people the APC gene has anti-tumour properties but when it is altered this ability is lost and it can allow tumours to begin by switching on a molecule called c-Myc. With a grant from AICR Dr Sansom is investigating whether switching off the c-Myc molecule could stop bowel cancers from growing in mice with altered APC genes.
Grant Holder: Professor Rohini Kuner
Institution: University of Heidelberg, Germany
Grant Award: £163,941 for 2 years
Project Title: Investigating ways to stop cancer pain
Many people with cancer that has spread to the bones also suffer from debilitating pain which can lead to a very poor quality of life. Sadly cancer pain works through a unique mechanism which is still poorly understood. With a previous AICR grant using animal models which mimic the spread of cancer to the bones, Professor Kuner discovered that two molecules called G-CSF and GM-CSF were involved in causing this cancer pain. Professor Kuner is now building on these findings and trying to find potential drugs which could block the effect of these molecules and therefore stop the pain.
Grant Holder: Dr Maria S Soengas
Institution: Spanish National Cancer Centre, Spain
Grant Award: £197,100 for 3 years
Project Title: Developing new treatments for skin cancer
Dr Soengas is working on the most dangerous type of skin cancer called melanoma. Cancer occurs when our DNA becomes damaged, for example after long term exposure to UV light from the sun. The damaged DNA can cause the cells to begin growing and dividing rapidly in an uncontrolled manner, forming a tumour. With a grant from AICR Dr Soengas is investigating molecular structures called ‘nanoparticles’ that recognize melanoma cells and encourage them to die by digesting themselves. The Soengas group has already tested this approach on cells grown in the laboratory, as well as in melanoma cancer models. Now they aim to develop ways to visualize the nanoparticles inside animals and people. To do this they will use various systems, including small samples of tumours taken from melanoma patients. Dr Soengas hopes that her results could one day lead to clinical trials to develop better treatments for melanoma and possibly other types of cancer.
Grant Holder: Associate Professor Louise E Purton
Institution: St Vincents Institute of Medical Research, Australia
Grant Award: £186,214 for 3 years
Project Title: The role of the microenvironment in leukaemia
Myeloproliferative syndromes (MPS) are a group of blood diseases that can develop into leukaemia. However, it is not yet clear exactly how some MPS develop into leukaemia and patients often respond poorly to standard cancer therapies. Dr Purton has recently developed two mouse models which indicate that the bone marrow microenvironment may be involved in MPS and the progression into leukaemia. The bone marrow microenvironment consists of cells that are not blood cells but help in making blood cells and include bone cells and blood vessels. Dr Purton is using her AICR grant to investigate how the bone marrow microenvironment contributes to blood diseases such as MPS and leukaemia so that better treatments can be developed for these patients in the future.
Grant Holder: Dr Tanya J Shaw
Institution: St Georges University London, UK (England)
Grant Award: £78,584 for 2 years
Project Title: Defining the relationship between ovulation and ovarian cancer
Worldwide, an estimated 125,000 women die of ovarian cancer each year but the causes of the disease are still unknown. A current theory is that the constant injury and repair caused by ovulation can cause cancer of the ovaries. During ovulation an egg is released from the ovary, which involves a 'wound' in the layer of tissue overlying the egg. It is thought that in some women this repeated injury and healing eventually causes the cells in the tissue lining the ovarian surface to change and become cancerous. Further evidence that supports this hypothesis is the fact that reducing the number of ovulations a woman has during her lifetime, for example through the use of oral contraceptives, decreases their risk of ovarian cancer. Dr Shaw is using her AICR grant to investigate the damage caused to the ovarian tissue when the egg is released and how it is then repaired, including the time taken and any inflammation that may occur. By looking at pre-cancerous changes and ovarian tumours she hopes to understand the relationship between the injury, the healing process and ovarian cancer.
Grant Holder: Dr Gioacchino Natoli
Institution: Istituto Europeo di Oncologia, Italy
Grant Award: £170,220 for 3 years
Project Title: The immune system and cancer
Our immune system is made up of cells that have the ability to recognise foreign molecules – such as those found on bacteria and viruses. Once a foreign body has been detected, the immune system cells are able to attack and kill it. Macrophages are a type of immune system cell which are often found at wounds or sites of infection where they help recruit other cells to fight the foreign molecules. In solid tumours however there are a different type of macrophage called tumour-associated macrophages (TAMs) which play a very different role. Instead of helping to fight infections, tumour-associated macrophages release molecules which encourage the growth of blood vessels to supply the tumour and attract other molecules which help form the shape of the tumour. The information which determines whether they are ‘good’ macrophages or ‘bad’ tumour associated macrophages is encoded in the genes. Dr Natoli is therefore using his AICR grant and cutting edge techniques to investigate at a genetic level why these two cell types are so similar yet have such different activities.
Grant Holder: Professor Juergen Kuball
Institution: University Hospital Utrecht, Netherlands
Grant Award: £246,665 for 3 years
Project Title: How does our immune system fight cancer?
Our immune system is made up of cells that have the ability to recognise foreign molecules – such as those found on bacteria, viruses. It has long been suspected that our immune system also has the potential to attack and kill cancer cells. Professor Kuball is investigating how the immune system can detect and kill cancer cells. His findings could be important for the development of new cancer treatments in the future.
Grant Holder: Professor Marco Foiani
Institution: IFOM The FIRC Institute of Molecular Oncology Foundation, Italy
Grant Award: £148,620 for 3 years
Project Title: Learning lessons from yeast
Professor Foiani is using his AICR grant to investigate how two cell processes - DNA copying and DNA transcribing (involved in making new proteins) work with each other. It is important that these processes do not negatively affect each other or it could lead to breaks in the DNA and the cell becoming cancerous. Professor Foiani is carrying out the work in yeast cells, which are very similar to human cells but less complicated and easier to work with. They therefore provide an ideal opportunity to understand biological problems before they can be studied directly in humans.
Grant Holder: Professor Pier Guiseppe Pelicci
Institution: Istituto Europeo di Oncologia, Italy
Grant Award: £121,500 for 3 years
Project Title: Why are cancer stem cells so dangerous?
Within our bodies, amongst the many different types of cells are tiny populations of cells called stem and progenitor cells. Stem cells are a kind of 'starter cell' which can multiply and generate copies of themselves and also produce a wide variety of more "mature" cells. The progenitor cells, instead, are more specific than stem cells and can only turn into predetermined cell types. Therefore, only stem cells are able to generate a whole tissue, e.g. the mammary tissue in breasts. Normal stem cells have an upper limit on the number of times they can divide; what makes cancer stem cells so dangerous is that something causes this upper limit to increase so that they can proliferate out of control and generate a whole tumour. Professor Pelicci has found that stem cells and progenitor cells react differently when cancer causing genes are turned on or when DNA becomes damaged and he is now using his AICR grant to investigate this difference. Professor Pelicci hopes his research will shed light on what makes stem cells become cancerous. If we can stop this then in the future we may be able to stop tumours before they develop.
Grant Holder: Dr Mirna A. Perez-Moreno
Institution: CNIO, Spain
Grant Award: £175,069 for 3 years
Project Title: Understanding the link between skin cancer and the immune system
Skin cancer is conventionally separated into two categories: melanoma and non-melanoma skin cancer (NMSC). Non-melanoma skin cancer is the most common cancer in humans and unlike most cancers, which occur in people over 75, almost a third of malignant melanoma cases occur in people under 50. Skin is predisposed to cancer because it is constantly under attack from UV light from the sun, environmental hazards and injuries. Tissues with chronic wounds and inflammatory diseases are known to be more susceptible to cancer. Dr Perez-Moreno is using her AICR grant to investigate how the molecule p120-catenin is involved in preventing non-melanoma skin cancer. She will also be investigating if chronic inflammation, caused by the immune system, is also involved in the development of the disease in cells lacking p120-catenin.
Grant Holder: Professor Colin S Cooper
Institution: Institute of Cancer Research, UK (England)
Grant Award: £148,443 for 2 years
Project Title: Improving treatment for advanced prostate cancer patients
Prostate cancer cells normally only grow and divide in the presence of the male sex hormone androgen, which turns on a protein called the androgen receptor. The main drug treatments for prostate cancer work by blocking the production of androgens or the effect of androgens on the androgen receptor. However, although this treatment makes the cancer stop growing for a while the cells eventually become resistant to treatment. This means they become able to multiply despite the androgen-blocking treatments and the cancer comes back. One of the main reasons for this seems to be that the cells become extra sensitive to the remaining very low levels of androgens. Professor Cooper and his colleagues are investigating a process called androgen receptor ‘gene amplification’. Androgen receptor ‘gene amplification’ makes the cancer cells extra sensitive to androgens and has been reported in 20-30% of prostate cancers which continue to grow despite androgen blocking. Professor Cooper and his colleagues are now using an AICR grant to understand when the ‘gene amplification’ takes place. They will then assess whether it could be used as a marker to predict the outcome of the disease. They also hope to provide an initial assessment of whether prostate cancers which contain androgen receptor ‘gene amplification’ are more sensitive to treatment with the new drug abiraterone that can block the production of even very low levels of the androgens.
Grant Holder: Dr Lucas Waltzer
Institution: CNRS France
Grant Award: £157,000 for 3 years
Project Title: Understanding Leukaemia
Cancer is caused by changes to either the structure or activity of certain genes that control key activities within a cell such as cell growth and death. In some cancers, including leukaemia, one gene can become fused or ‘glued’ to the end of another one, creating a hybrid gene. In acute myeloid leukaemia (AML) the hybrid gene is called AML-ETO and it occurs when the AML1 gene fuses to the ETO gene. The AML1-ETO gene can turn on many cancer causing genes which causes the blood cells to grow and divide out of control and for leukaemia to develop. It is not currently known what factors control the activity of the AML1-ETO gene and this is the focus of Dr Waltzer’s AICR funded project. He is carrying out the work in fruit flies since fly cells are less complicated. Importantly, the genes that control the growth and death of fly cells are almost identical to those found in human cells, making their findings highly relevant to what goes on in the human body.