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Research projects funded

BCRT Research Strategy

We believe that investing in high quality research is essential to improving outcomes for those affected by primary bone cancer. Our Research Strategy outlines our objectives, the types of research we fund, and how the process works – click here to read more. This process is covered by our Conflicts of Interest statement, which you can read here.

We accept research applications twice annually, with the application deadlines being the last Friday in March, and the last Friday in September. For more information please contact Jennifer Houniet, Jennifer.houniet@bcrt.org.uk

Any concerns?

What makes a successful research outcome?

The success of a research project can be measured in several ways. Exciting research is published in research journals, and this acts to disseminate the information discovered, to help to inform other researchers and medical professionals.

Interesting results are also presented at national or international conferences, either as an oral presentation or as a poster presentation. These both help to stimulate discussion on the topic and help researchers to come up with new ideas.

It can take several years for a research project to reach a conclusion that is suitable for publication, and so these are often longer term aims. Another positive outcome from research is that good preliminary data, for example from a pump-priming grant, can invite larger funding grants from charities or research councils.


Click on the name of a researcher on the map below to find out more about their research.

Prof Sue Burchill, Leeds University Dr Ange Roelofs & Prof Michael Rogers, University of Aberdeen Dr Richard McNally, Newcastle University Prof Josef Vormoor, Newcastle University Prof Nicola Curtin & Evan Mulligan, Newcastle University Prof Jillian Birch, Manchester University Dr Paul Genever, York University Mr Lee Jeys, Royal Orthopaedic Hospital Birmingham Prof Farida Latif, Birmingham University Dr Kenneth Rankin, University of Newcastle Prof Nicholas Athanasou & Dr Helen Knowles, Oxford University Prof Agi Grigoriadis, King's College London Dr Sarah Welsh, University College Hospital, London Dr Rachael Windsor, University College Hospital, London Dr John Anderson, University College London Prof Adrienne Flanagan, Royal National Orthopaedic Hospital, Stanmore Ms Susie Pearce, University College Hospital, London Dr Teresa Coughlan, University of Nottingham Dr Britta Vormoor, Newcastle University Dr Neil Cross, Sheffield Hallam University Dr Sandra Strauss, University College London
Dr John Anderson, Senior Clinical Lecturer at the Institute of Child Health, University College London.
BCRT research grant 1
Project grant Development of clinical protocols for Ewing sarcoma treatment using gene transfer of T cell receptors £34,500
 

Aims of the research
This project aims to find a new way to make a patient's own immune system fight cancer, a technique called immunotherapy. Researchers have identified a gene called PAX3 which is switched on in Ewing's sarcoma cells, but is switched off in healthy cells. This makes PAX3 an ideal molecular target, as immune cells could seek out PAX3 and destroy the cells where it is present. However the first step would be to make the immune cells recognise PAX3 as a target. This project plans to take a blood sample, 'show' PAX3 to the immune cells in the blood, wait for the immune cells to respond to the PAX3 and then purify the PAX3-targetted immune cells from the blood. The immune cells showing the best response to PAX3 would be analysed and their PAX3-targetting genes copied. These copied PAX3-targetting genes could be added to a patient's own immune cells, so that the cells would then be able to seek and destroy the PAX3 tumour cells.

Outcomes from the research
This project, like many research projects that concern cutting-edge technologies and experimental techniques, ran into some technical problems and so the direction of the project changed slightly. PAX-3 proved to be a very difficult gene to work with and so the researchers changed to working on two other genes called TWIST and PRAME.

The research led to two research publications:

  • Gascoyne DM, Dunne J, Sebire NJ, Anderson J, Latchman DS; EWS/ETS proteins promote expression and regulate function of the homeodomain transcription factor BRN3A, Oncogene (2010) 29, 3134-2145

  • Yan M, Himnoudi N, Basu BP, Wallace R, Poon E, Adams S, Hasan F, Xue SA, Wilson N, Dalgleish A, Williams O, Anderson J; Increased PRAME antigen-specific killing of malignant cell lines by low avidity CTL clones, following treatment with 5-Aza-2'-Deoxycytidine, Cancer Immunology and Immunotherapy (2011) 60:1243-1255

Further funding awards:

  • CRUK Development Committee Funding Award via the New Agents Committee.

This means that BCRT's initial funding has led to a much larger grant that will enable the research into this technology to continue.

BCRT research grant 14
Pump-priming Investigation of functional inhibition of STAT3 in Ewing sarcoma family of tumours £17,500
 

Aims of the research
STAT3 is a gene that has been shown by other researchers to be a controller gene for signals that allow cancer cells to hide from a patient's immune system. This research team have already made several compounds (which are potential future drugs) that stop STAT3 from working, without affecting any other genes. This project will use these compounds in Ewing's sarcoma cells in the laboratory to see how well they work. The cells will be treated with the compounds and then monitored to see whether STAT3 has been successfully switched off and whether that blocks the effects of STAT3 on the immune system.

Outcomes from the research
This research found that STAT3 is present in around half of the Ewing's sarcoma samples that were studied. Targeting STAT3 in Ewing's sarcoma cells that had active STAT3 reduced the growth rate of the cells. The results from the research were promising and Prof Anderson's group is writing research grants to other funding bodies with the intention of continuing the research into how STAT3 can help cancer cells escape detection by the immune system.

Research publications:

  • Behjati s, Basu BP, Wallace R, Bier N, Sebire N, Hasan F, Anderson J; STAT3 Regulates Proliferation and Immunogenicity of the Ewing Family of Tumours In Vitro, Sarcoma Volume 2012 Article ID 987239.

Dr Richard McNally, Reader in Epidemiology at Newcastle University
BCRT research grant 2
Pump-priming An epidemiological study of bone tumours in children and young adults £29,985
 

Aims of the research
This project aims to uncover factors that increase a person's risk of developing primary bone cancer, by analysing data about bone cancer patients and trying to spot aspects of their lives that are shared amongst patients. Dr McNally points out that while the number of primary bone cancer cases has not increased or decreased, there are geographical areas and points in time where more cases are seen. This indicates that there could be an environmental 'cause' for the disease in these places and times. This research project has two parts: firstly a detailed analysis of all research papers about primary bone cancer incidence to examine what risk factors have been proposed before. The second part is to use data from the cancer registries (centres that record information about all cases of cancer) to look at incidence patterns, trends and survival of primary bone cancers in children and young adults.

Outcomes from the research
This project found interesting and useful information about the incidence and survival of primary bone cancers. Despite an overall increase in the number of children's cancers in the last 40 years, the incidence of primary bone cancers have remained stable. Survival rates for Ewing's sarcoma have improved slightly but not for osteosarcoma. Information garnered has provided a fuller picture of where and when primary bone cancers have occurred. In conclusion the researchers felt that any connection between fluoride in drinking water and primary bone cancer needed further investigation.

BCRT research grant 8
Pump-priming Environmental contributions to the aetiology of bone tumours in young people: small area analysis £30,601
 

Aims of the research
This second grant awarded to Dr McNally continues his work into identifying the causes of primary bone cancer. This project aims to answer one specific question: Could the fluoride added to drinking water increase the risk of primary bone cancer? Other small research studies have tried to answer this question but the answer is still not clear. This study will look at the variation in rates of bone cancer incidence across Great Britain and then compare that to the levels of fluoridation in the water. Different age-groups, types of primary bone cancer and patient gender will be analysed to get a more complete picture.

Outcomes from the research
No statistically significant link between fluoride in drinking water and osteosarcoma or Ewing's sarcoma was found. The research did also investigate whether there was any link between primary bone cancer incidence and social deprivation. Interestingly, Ewing's sarcoma incidence rates were decreased in more socially deprived backgrounds, a reversal of the situation with many of the lifestyle-associated cancers where social deprivation is associated with higher incidence of cancer. No link was found between osteosarcoma and social deprivation.

BCRT research grant 24
Project grant The epidemiology of osteosarcoma and Ewing's sarcoma in children and adults aged 0-49 years: Further investigations of aetiology and survival £30,309
 

Aims of the research
Continuing the theme of looking for environmental factors that might increase a person's risk of developing primary bone cancer, this project builds on the data from previous studies. A previous project by Dr McNally's group showed that the risk of developing childhood Ewing's sarcoma or osteosarcoma increased in areas where there were higher levels of car-ownership. In addition there was decreased risk of Ewing's sarcoma in areas of higher population density. These two observations led to the hypothesis that living in rural areas might increase the risk of these two primary bone cancers. Could this be due to some aspect of agriculture? Alternatively could this be due to faster diagnoses of bone cancer in urban areas?

Outcomes from the research
This project is still on-going.

Research publications from BCRT funded projects:

  • Eyre , Feltbower RG, Mubwandarikwa E, Jenkinson HC, Parkes S, Birch JM, Eden TO, James PW, McKinney PA Pearce MS, McNally RJ [2009]: Incidence and survival of childhood bone cancer in Northern England and the West Midlands, 1981-2002. British Journal of Cancer 100(1) 188-193

  • Eyre R, Feltbower RG, Mubwandarikwa E, Eden TO, McNally RJ [2009]: Epidemiology of bone tumours in children and young adults. Pediatric Blood and Cancer 53(6) 941-952.

  • Eyre R, Feltbower RG, James PW, Blakey K, Mubwandarikwa E, Forman D, McKinney PA, Pearce MS, McNally RJ [2010]: The epidemiology of bone cancer in 0 – 39 year olds in northern England, 1981 – 2002. BMC Cancer 10(1) 357.

  • McNally RJ, Blakey K, Parslow RC, James PW, Gomez-Pozo B, Stiller C, Vincent TJ, Norman P, McKinney PA, Murphy MF,Craft AW, Feltbower RG. [2012]: Small area analyses of bone cancer diagnosed in 0-49 year olds from Great Britain provide clues to aetiology. BMC Cancer

Presentations at research conferences:

  • Blakey K, Feltbower RG, Parslow RC, James PW, Gomez-Pozo B, Stiller C, Vincent TJ, Norman P, McKinney PA, Murphy MF, Craft AW, McNally RJQ [2010]: Demographic analyses of primary bone cancer in 0-49 year olds in Great Britain, 1980-2005: a small-area approach [abstract]. Journal of Epidemiology and Community Health 2010;64(Supplement 1) A1-A2 abstract no. 003.
    Presented at the Society for Social Medicine 54th Annual Scientific Meeting, September 2010.

  • Blakey K, Feltbower RG, Parslow RC, James PW, Gomez-Pozo B, Stiller C, Vincent TJ, Norman P, McKinney PA, Murphy MF, Craft AW, McNally RJQ [2010]: Flouride and bone cancer: is there a link? Small-area analyses of primary bone cancer in 0-49-year-olds in Great Britain, 1980-2005 [abstract]. Journal of Epidemiology and Community Health 2010;64(Supplement 1) A2 abstract no. 004.
    Presented at the Society for Social Medicine 54th Annual Scientific Meeting, September 2010.

  • Blakey K, Feltbower R, Parslow R, James P, Gomez-Pozo B, Stiller C, Vincent T, Norman P, McKinney P, Murphy M, Craft A, McNally R [2011]: Primary bone cancer in 0-49 year olds in Great Britain, 1980-2005 and fluoride in drinking water: a case of inequalities? Journal of Epidemiology and Community Health 65(S1) A93-A94.
    Presented at the IEA World Congress of Epidemiology, August 2011.

  • Blakey K, Feltbower R, Parslow R, James P, Gomez-Pozo B, Stiller C, Vincent T, Norman P, McKinney P, Murphy M, Craft A, McNally R [2011]: Demographic analysis of osteosarcoma and Ewing sarcoma family of tumours in 0-49 year olds in Great Britain, 1980-2005: a small area approach. Journal of Epidemiology and Community Health 65(S1) A94.
    Presented at the IEA World Congress of Epidemiology, August 2011.

Professor Agi Grigoriadis, Professor of Bone and Cartilage Biology at King's College London
BCRT research grant 4
Project grant Identifying a novel role for deregulated Fibroblast Growth Factor Receptor Signalling in the growth control of human osteosarcoma cells £29,720
 

Aims of the research
Prof Grigoriadis' previous work has shown that a gene called c-fos was important in the development of healthy bones, but that when c-fos was not kept in check it could cause osteosarcoma. C-fos is a 'controller' gene that can control the activity of many other genes. Two such genes under the control of c-fos are FGFR1 and FGFR3, both of which are both able to make cells grow and divide. The research team looked at tumour samples of human osteosarcoma and found that FGFR1 and FGFR3 are both active in osteosarcoma. This research project intends to find out how FGFR1 and FGFR3 are playing a role in osteosarcoma by looking inside osteosarcoma cells grown in the laboratory.

BCRT research grant 9
Project Targeting FGF receptor signalling for the treatment of osteosarcoma £29,720
 

Aims of the research
This project aims to build on the results from the previous project by taking a more in depth look at FGFR1 and FGFR3 in osteosarcoma. In this project the roles of FGFR1, FGFR2, FGFR3 and FGFR4 will be analysed to see which of this family of genes is most important in osteosarcoma. The FGFR genes will be blocked to see whether this could provide a therapeutic strategy in osteosarcoma. The effects of blocking FGFR signalling will be tested in cells and in laboratory-based tumour models.

Outcomes from the research
The results of the experiments in this project showed that FGFR1 and its signalling partner genes are dis-regulated in osteosarcoma. During this project a successful international collaboration with a laboratory in Spain was set up so that expertise and equipment can be shared between laboratories.

Further funding awards:
Further funding for this research was secured from the Guy's, King's and St Thomas's Trust Charity on the basis of the results achieved through the BCRT-funded project.

Presentations at research conferences:
Poster presentation at British Association of Cancer Research Conference 2010
Poster presentation at American Society of Bone and Mineral Research 2009

Professor Adrienne Flanagan, Professor of Musculo-Skeletal Pathology at University College London
BCRT research grant 5
Project Cancer stem cells in osteosarcoma: potential for new prognostic markers and treatment £28,800
 

Aims of the research
The concept of 'cancer stem cells' has revolutionised how we think about cancer in recent years. The idea is that cancer can't be caused by any cell in the body developing mutations in its DNA, instead that there cancer occurs when a stem cell becomes mutated, becoming a so-called 'cancer stem cell'. These cancer stem cells can grow and grow without the normal growth-control genes being activated. The concept of cancer stem cells has been controversial however, and there are many technical difficulties in identifying cancer stem cells. In this project Professor Flanagan aims to look in osteosarcoma tumour samples for evidence of cancer stem cells. Also tumour cells will be analysed and the stem cells extracted. These stem cell groups will be studied and information about their growth and other characteristics gathered. Information about these cancer stem cells might help to guide research to more targeted treatments in the future.

Outcomes from the research
This study reached some interesting conclusions on the involvement of cancer stem cells in osteosarcoma. 200 osteosarcoma tumours were examined for whether certain stem-cell genes were switched on or off, and the proportion of stem cells per sample was compared to how well the tumour responded to chemotherapy, as it has been proposed that the stem cell portion of tumours is responsible for the failure of the tumour to respond to these drugs. The researchers could not find any link between the number of stem cells present and whether the osteosarcoma was a good or poor responder to chemotherapy.

Research publications from BCRT funded research:

  • Duhamel LA, Ye H, Halai D, Idowu BD, Presneau N, Tirabosco R, Flanagan AM.
    Frequency of Mouse Double Minute 2 (MDM2) and Mouse Double Minute 4 (MDM4) Amplification in Parosteal and Conventional Osteosarcoma Subtypes, Histopathology 2012 Jan;60(2):357-9.
BCRT research grant 23
Project Biobank technician for three major osteosarcoma genetic projects involving patients' samples (tumour and normal tissue) £29,600
 

Aims of the research
This grant was awarded to fund a research technician post in the laboratory, to process samples for three very exciting, and externally funded, projects. The technician will create a 'biobank' of samples from osteosarcoma patients. A biobank is a large collection of samples such as tumour biopsies, DNA or blood samples. The biobank can then be used by researchers to analyse a large number of samples at once, which means that the researchers get a better picture of the disease. The samples from this biobank will be used in three projects: Firstly the DNA changes in the osteosarcoma samples will be analysed to find out which genes are altered in osteosarcoma. Secondly, the DNA changes in each patient's tumour will be analysed and the researchers will see whether these changes are also present in dead cells in the blood. If the DNA changes could be detected, then this might lead to a simple blood test for osteosarcoma. The third project is a study of the inherited DNA in osteosarcoma patients, to see whether there are any inherited gene-changes that might increase the risk of osteosarcoma.

Outcomes from the research
Significant progress was made in all three of the projects outlined in this grant.

Project 1:
The genetic make-up of 150 patients’ osteosarcoma samples was analysed at the world-leading Wellcome Trust Sanger Institute in Cambridge, UK. This has generated a huge amount of data, which is currently being analysed by researchers. Prof Flanagan is hoping to submit the results of this for publication in early 2014.

Project 2:
Blood samples have now been taken from almost 100 osteosarcoma patients, plus 90 chondrosarcoma patients, 22 Ewing’s sarcoma patients and 20 other bone tumour patients. These samples have been taken before, during and after treatment, and so it is hoped that the researchers can find a way of detecting not just the presence of a bone tumour, but how it is responding to therapy. This research is expected to take up to a further 2 years due to the complexity of the analysis.

Project 3:
DNA samples from 221 osteosarcoma patients have been send for genetic analysis to look at the patterns of genes that these patients have inherited, to try to find common DNA features that could be responsible for causing osteosarcoma. The results from this analysis have been presented at the American Association of Cancer Research conference in April 2013, and will be published in the prestigious journal Nature Genetics in summer 2013.

Research publications and presentations to date from this BCRT funded research:

  • AACR Platform Presentation, April 2013. Genome-wide association study identifies novel loci associated with osteosarcoma

  • Sharon A. Savagei et al Genome-wide Association Studv Identifies Novel Loci Associated with osteosarcoma (submitted to Nature Genetics, 2013)

  • Amary MF, Damato S, Halai D, Eskandarpour M, Berisha F, Bonar F, McCarthy S, Fantin VR, Straley KS, Lobo S, Aston W, Green CL, Gale RE, Tirabosco R, Futreal A, Campbell P, Presneau N, Flanagan AM (2011) Ollier disease and Maffuci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. Nature Genet. 43 :T262-1265)

BCRT research grant 32
Project Generating osteosarcoma cell lines which will be analysed as part of the International Cancer Genome Consortium (ICGC) – bone tumour project. £13,601.14
 

Aims of the research

This grant will pay for laboratory equipment that will allow new osteosarcoma ‘cell lines’ to be established in Professor Flanagan’s laboratory.

When a tumour sample is donated by a patient, different aspects of that sample can be studied, such as the DNA in the cells tumour cells can be analysed to see whether any genes are mutated, the on/off switching of certain genes can be studied, or the structure and cellular make-up of the tumour can be examined by looking down a microscope.

Another way of using a tumour sample for research is to use special laboratory conditions to grow the cells from the tumour. Cells that are grown from a tumour sample, but then kept growing for a long time after they’ve left the tumour sample, are called a ‘cell line’. Cell lines are really useful because the cells keep growing so lots of experiments can be done. Researchers can use these cell lines to see how the tumour cells respond to chemotherapy, and to try out new anti-cancer treatments.

The cell lines grown from using this research grant will be used for research that forms part of an international study into the genetics of osteosarcoma.

Outcomes from the research
This information will be updated when the project has finished.

Dr Rachael Windsor, Consultant Paediatric Oncologist at the Royal Marsden Hospital
BCRT research grant 3
Pump priming A pilot pharmacogenetic study of the influence of cytotoxic metabolising gene polymorphisms on toxicity and outcome in resectable osteosarcoma £30,000
 

Aims of the research
It is well known that some patients respond to chemotherapy better than others, and that this has a huge impact on the outcome of treatment. There are a number of genes that can impact on response to chemotherapy drugs, including those drugs used in the treatment of osteosarcoma. In this study Dr Windsor will analyse blood samples from osteosarcoma patients to find out whether certain gene changes can impact on how well the patients respond to osteosarcoma treatment, and what kind of side-effects are experienced from the drugs. While there is evidence that changes in specific genes affect how well patients with some adult tumours and leukaemias respond to chemotherapy, nobody has looked in osteosarcoma patients before.

BCRT research grant 11
Project (extension to funding) A pilot pharmacogenetic study of the influence of cytotoxic metabolising gene polymorphisms on toxicity and outcome in resectable osteosarcoma £41,956
 

Aims of the research
This grant was given to extend the grant funding from the previous project.

Outcomes from the research
This project looked at 35 specific changes in 20 genes that are known to be related to both the tumour response and the negative side-effects of chemotherapy drugs used in osteosarcoma. The results showed that there certain combinations of gene changes – so-called 'genetic profiles' – were associated with different outcomes and different toxic responses. This study needs to be expanded before the data can be used clinically, in order to examine greater numbers of patients. The researchers conclude that with more work this type of analysis might be used to optimise the treatment of different patients so that they can be treated more effectively and without such serious side-effects.

Research publications:

  • Windsor RE, Strauss SJ, Kallis C, Wood NE, Whelan JS; Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma: a pilot study; Cancer. 2012 Apr 1;118(7):1856-67

  • Windsor R, Strauss SJ, Seddon B, Whelan J. Experimental Therapies in Ewing's Sarcoma. Expert Opinion On Investigational Drugs 2009; 18(2): 143-159

Presentations at research conferences:

  • Windsor R, Strauss SJ, Wood N, Whelan J. A pilot pharmacogenomic study of the influence of cytotoxic target and metabolising gene polymorphisms on toxicity and response in osteosarcoma. 22nd Annual Meeting of the European Musculo-Skeletal Oncology Society, Germany 2009. Poster and abstract

  • Windsor R, Strauss SJ, Seddon B, et al. A pilot pharmacogenomic study of the influence of cytotoxic and metabolising gene polymorphisms on toxicity and response in resectable osteosarcoma. Cold Spring Harbor Laboratories Pharmacogenomics Meeting, USA 2008. Poster and abstract

Professor Nicholas Athanasou, Professor of Muskuloskeletal Pathology at the University of Oxford; and Dr Helen Knowles, Principle Investigator at the University of Oxford
BCRT research grant 6
Pump priming Effect of hypoxia on growth, apoptosis and angiogenic capacity if osteosarcoma and Ewing's sarcoma cells: regulation by Hypoxia-Inducible Factor £27,213
 

Aims of the research
Hypoxia is the term given to when living cells are getting less oxygen than they need. This is a common situation in cancer, where the middle of a tumour can sometimes be far away from the nearest oxygen-carrying blood vessel. Whereas intuitively it might seem like this lack of oxygen would make the tumour weaker and more susceptible to anti-cancer treatment, in fact, from evidence in breast cancer and other tumour types it seems that hypoxia makes tumour cells harder to kill. One way that this happens is through the activation of a gene multi-functional gene called Hypoxia-Inducible Factor 1 and 2, or HIF1 and HIF2, which are switched on in hypoxia. This project will investigate the effects of the HIF genes and hypoxia on osteosarcoma and Ewing's sarcoma cells in the laboratory, and find out which of the two genes is most active in bone cancer. Also the researchers will look at osteosarcoma and Ewing's sarcoma tumour samples to see whether these genes are switched on in primary bone cancer tumours, and which genes they control.

Outcomes from the research
HIF1a was found in most of the Ewing's sarcoma tumours tested and a preliminary set of osteosarcomas, all in areas where there was low oxygen and high cell death. In Ewing's sarcoma cells HIF1a and HIF2a were switched on in response to low oxygen, and interestingly HIF2a was switched on in response to low glucose. In osteosarcoma HIF1a and HIF2a were similarly switched on in response to low oxygen but glucose levels did not switch on HIF1a or HIF2a. A collaboration with a European laboratory has been set up to try to find out what these changes mean and whether they have any effect on disease progression or could lead to any therapeutic approaches.

Research publications:

  • Helen J Knowles, Karl-Ludwig Schaefer, Uta Dirksen, Nicholas A Athanasou. Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor. BMC Cancer (2010), 10:372
    http://www.biomedcentral.com/1471-2407/10/372

Presentations at research conferences:

  • Phenotypic effects of hypoxia and Hypoxia-Inducible Factor in Ewing's sarcoma, Knowles & Athanasou. Oral presentation: Bone Research Society conference, London (June 2009)

  • Hypoxia, Glucose-Deprivation and Hypoxia-Inducible Factor: phenotypic effects in Ewing's sarcoma, Knowles & Athanasou. Presented at the American Society of Bone and Mineral Research 2009 annual meeting (Sept 2009)

Professor Josef Vormoor, Sir James Spence Professor of Child Health, Newcastle University
BCRT research grant 7
Pump priming Molecular mechanisms of organ-specific Ewing's sarcoma metastasis £31,772
 

Aims of the research
Metastasis is the medical term for the spreading of cancer from the organ/tissue where it first started, to another place in the body. The tumour cells spread around the body through the blood vessels or the lymphatic system and then settle in another place, forming a secondary tumour. The presence of metastasis in primary bone tumours is a measure of how serious the disease is, as tumours that have metastasised are harder to treat. In Ewing's sarcoma there is a clear pattern whereby if a patient's cancer spreads from the primary site to another bone, the disease is very much harder to treat than in patients whose cancer has spread to the lungs. This research project is designed to find out what the difference is between tumours that spread to the bones and tumours that spread to the lungs. The gene-activity patterns of these two tumour types will be compared to find out what the molecular differences are.

Outcomes from the research
In order to understand the differences between lung and bone metastases the researchers first needed develop a reliable technique for detecting metastases. The researchers found that using a combination of FDG-PET and CT scanning allowed the detection of secondary tumours better than MRI scanning. This is an essential first step in understanding how metastases form.

Presentations at research conferences:

  • Knizia H, Batey M, Unland R, Korsching E, Dirksen U, Jürgens H, Heidenreich O, Hotfilder M, Hempel G, Vormoor J. Identifying Cellular Mechanisms of Organ-Specific Metastasis of Ewing's Sarcoma. Abstract for BACR/RSM Oncology Section/APS Joint Meeting: 'Preclinical models, biomarkers and targeted therapy', November 2008: Selected for oral presentation and poster

  • M.A.Batey, H Knizia and J Vormoor. Preclinical Modelling of Ewings Sarcoma Poster presentation and general discussion given at the BCRT Annual Supporters Conference, Sopwell House Hotel, St Albans, June 2009

Professor Jillian Birch, Cancer Research UK Professional Fellow, Director of Cancer Research UK Paediatric and Familial Cancer Research Group
BCRT research grant 10
Project grant A pilot study of the aetiology and genetics of bone tumours in children, teenagers and young adults £47,555
 

Aims of the research
Professor Birch's project focuses on looking for the causes of osteosarcoma and Ewing's sarcoma. This study is a small 'trial run' preparing for a larger international study to find any environmental or genetic factors which increase the risk of developing osteosarcoma or Ewing's sarcoma. Patients diagnosed with osteosarcoma or Ewing's sarcoma at Manchester or Leeds will be asked to take part in the study. The patient and their parents will give blood or saliva samples (to provide DNA) and the patient's medical records will be analysed. The patient and their parents will be interviewed to find out about the patients early years – their growth before and after birth and about lifestyle factors such as diet, activity and any illnesses at crucial ages. This small study will be used to improve the process ready for a larger, international study using these methods.

Outcomes from the research
This project is still on-going.

Professor Susan Burchill, Professor of Paediatric and Adolescent Cancer Research, Leeds University
BCRT research grant 13
Project grant Investigating the combination of fenretinide and TRAIL receptor agonists in the Ewing's sarcoma family of tumours £49,591
 

Aims of the research
Fenretinide is an anti-cancer drug that has shown cancer-killing properties when tested on Ewing's sarcoma cells in the laboratory and promising results in a phase 1 clinical. This project aims to investigate whether combining fenretinide with another type of treatment, called a TRAIL agonist, might improve the treatment further. Neither of the two treatments alone appears to affect healthy cells, and so this study would check to see whether the combination of treatments would still only affect cancer cells or whether the side-effects might increase with the combined treatment. This would help to guide further research into these drugs.

Outcomes from the research
Fenretinide and the TRAIL agonist drug were added to Ewing's sarcoma cells and the researchers counted the number of cells that were killed by the drugs. As predicted, the combination of the two drugs killed more Ewing's sarcoma cells than either one of the drugs separately. However, of the four different types of Ewing's sarcoma cells tested, one type did not respond at all to the TRAIL agonist drug. Therefore the results of these experiments were positive, but highlight the fact that not all tumours respond to drugs in the same way.

Research publications:

  • • White DE, Burchill SA; Fenretinide-dependent upregulation of death receptors through ASK1 and p38α enhances death receptor ligand-induced cell death in Ewing's sarcoma family of tumours.
    British Journal of Cancer. 2010 Oct 26;103(9):1380-90. Epub 2010 Sep 28.

BCRT research grant 15
Project grant Overcoming the challenges of studying telomerase biology in clinical samples; towards understanding tumour heterogeneity, telomerase and clinical significance in the Ewing's sarcoma family of tumours £38,212
 

Aims of the research
Telomerase is a gene that controls how many times a cell can divide. In healthy cells telomerase is not active, and therefore after a cell has reached its maximum number of cell divisions the cell will die. In many cancers telomerase is activated and so the cancer cells are able to continue to divide indefinitely. In this study, tumour samples from Ewing's sarcoma patients will be analysed and compared to healthy cells to see how active telomerase is in the tumours. Also the number of cells per tumour that have active telomerase will be counted, to give an idea of the level of variation within one tumour. This will give researchers a better understanding of telomerase in Ewing's sarcoma would be crucial if therapies designed to target telomerase were to be developed.

Outcomes from the research
This study was successful in optimising a number of experimental techniques, including how to measure telomerase activity in tumour samples and how to assess the number of cells that are actively dividing. The research found that the higher the proportion of cells in the tumour that were dividing, the worse the prognosis for the patient. This test could be used in routine pathology to assess the grade of a tumour.

BCRT research grant 19
Pump priming Modelling the early development of the Ewing's sarcoma family of tumours using IPS technology; a paradigm for unravelling the malignant phenotype £66,904
 

Aims of the research
The process by which a cell becomes cancerous is known to depend on the cell acquiring a number of changes to the cell's genes (mutations), and subsequent changes in the cell's behaviour. These behaviour changes include escaping the cell's normal control system thus being able to divide more often and for longer than they should. The exact sequence of events in how cells achieve this is not yet clear. In this project, Professor Burchill and her team want to be able to identify exactly which steps have to occur for a bone cell to become Ewing's sarcoma. In order to do this they are going to use 'IPS (Induced Pluripotent Stem cell) technology'. This means that they will take a cancer cell and set it in rewind, before playing it back to watch the steps in becoming cancerous. Ewing's sarcoma cells will be treated in such a way as genetically 'wipe' the cancer programming – making them into stem cells. Then the group will then step-by-step treat the cells to coax them back into being bone cancer cells. The gene changes in this 'return to cancer' will be measured, shedding light on the processes involved in the first steps of Ewing's sarcoma.

BCRT research grant 25
Project grant (extension) Modelling the early development of the Ewing's sarcoma family of tumours using IPS technology; a paradigm for unravelling the malignant phenotype £56,515
 

Aims of the research
To complete the studies planned in grant number 19.

Outcomes from the research
This project is still on-going.

BCRT research grant 36
Project grant Genotype and phenotype of self-renewing cancer-initiating Ewing's sarcoma cells £74,345
 

Aims of the research

Ewing’s sarcoma is an aggressive, high-grade primary bone cancer that mainly affects children, teenagers and young adults. Treatment for Ewing’s sarcoma involves a combination of surgery, chemotherapy and radiotherapy, and yet despite this comprehensive treatment the cancer returns in some patients.

Recent research suggests that in the case where the cancer relapses (comes back), one particular sub-set of cancer cells are responsible. These sub-set of cells are called the ‘cancer stem cells’ or CSCs. CSCs are the driver cells of the tumour – these are the cells that can grow fastest and which learn to beat chemotherapy and radiotherapy.

This project aims to find ways to identify CSCs within Ewing’s sarcoma tumour samples. This will involve identifying the gene-profile (‘genotype’) and the functional attributes (‘phenotype’) of the CSCs. Once we can learn how to identify the CSCs, further research can be conducted to find new ways to beat this dangerous group of cells.

Outcomes from the research
This information will be updated when the project has finished.

Dr Anke Roelofs, Project Manager at the University of Aberdeen; and Professor Michael Rogers, non-clinical Professor at the University of Aberdeen
BCRT research grant 12
Project The role of tumour-associated macrophages in the anti-osteosarcoma effects of bisphosphonates £29,942
 

Aims of the research
Bisphosphonates are drugs that stop the destruction of bone. They are given to osteoporosis patients to try to prevent their bones from thinning, and bisphosphonates are also prescribed for primary bone tumour patients to stop bone around the tumour being damaged and destroyed by the cancer. This research group have been able to watch for the first time how bisphosphonates work. They used bisphosphonate molecules that were tagged with bright colours, and watched to see which cells absorbed the colours. As well as the osteosclasts (the cells that usually eat away old bone to be replaced) the bisphosphonates were taken up by immune cells called macrophages. The macrophages near tumours actually help the tumour to grow by spreading growth signals and helping cells to break away to form secondary tumours. This means that as bisphosphonates inhibit the macrophages as well as the osteoclasts, they are providing a two-pronged action that limits bone damage and slows tumour growth. The aim of this project is to properly characterise the anti-cancer benefits of bisphosphonates in order to better understand how they can be used against primary bone cancers.

Outcomes from the research
This research proved that macrophage cells do indeed take up bisphosphonates, while tumour cells do not. The pro-tumour activities of the macrophages were blocked by the bisphosphonates. However, a high dose of bisphosphonates was required to have this effect. No decrease in the number of macrophages in tumours was seen. Further research is needed to clarify exactly what kind of effect the bisphosphonates have on tumour cells.

International collaboration
This project was carried out in collaboration with scientists at the University of southern California in America, the University of Kuopio in Finland and at INSERM, the French national institute of health and medical research, in Nantes. The French collaborating group have continued this BCRT-initiated research using their own research funding.

Research publications:

  • Roelofs AJ, Thompson K, Ebetino FH, Rogers MJ, Coxon FP. Bisphosphonates: molecular mechanisms of action and effects on bone cells, monocytes and macrophages.
    Current Pharmaceutical Design. 2010;16(27):2950-60. Review.

Presentations at research conferences:

  • American Society of Bone and Mineral Research, 2009

  • International Meeting On Cancer Induced Bone Disease, 2009

Dr Paul Genever, Senior Lecturer at the University of York
BCRT research grant 16
Pump priming Analysis of 3D mesenchymal stem cell-induced cytotoxicity in osteosarcoma and Ewing's sarcoma cell lines £28,315
 

Aims of the research
Mesenchymal stem cells (MSCs) are the class of stem cells that can go on to make cells of the bone, cartilage, muscle or fat. MSCs are widely studied because researchers hope to be able to grow new bone or cartilage for patients who have been injured or have damage caused by osteoporosis or cancer. MSCs are very powerful cells in the body and release many molecular signals that tell surrounding cells what to do and how to behave. Some of the signals that are released by the MSCs when they are grown in 3D clusters in the laboratory seem to be able to kill tumour cells whilst leaving healthy cells unharmed. One of these anti-tumour signals is called IL-24. This project seeks to identify how IL-24 works to kill cancer cells, and work out whether IL-24 or MSCs could ever be used to treat primary bone cancers.

Outcomes from the research
The production of IL24 by the MSCs was confirmed and the experiments showed that the MSCs were able to produce a signal that killed sarcoma cells. However, when synthetic IL24 was added to the cells it was found that a very high concentration of IL24 was needed to kill sarcoma cells, and that this killed healthy cells as well. This suggested that IL24 might not be the cancer-killing signal. This research will continue in order to find clearer answers.

Presentations at research conferences:

  • Supriya Sachamitr, Jess E. Frith and Paul G. Genever. Dynamic three-dimensional mesenchymal stem cells selectively induce cancer cell death. 4th Annual Mesenchymal Stem Cell Meeting, Leeds, 2010.

  • Supriya Sachamitr, Jess E. Frith and Paul G. Genever. Three-dimensional mesenchymal stem cells selectively induce cancer cell death. 3rd UK National Stem Cell Network Meeting, Nottingham, 2010.

  • Farinaz Afsari, Supriya Sachamitr, Jess E. Frith and Paul G. Genever. Using Adult Stem Cells to Treat Bone Cancer? BCRT 5th Patients' and Supporters' Conference, Manchester, 2011.

Professor Nicola Curtin, Professor of Experimental Cancer Therapeutics at Newcastle University; and Dr Evan Mulligan, Research Associate at Newcastle University
BCRT research grant 17
Pump priming An assessment of the PARP inhibitor AG-014699 £29,595
 

Aims of the research
PARP (Poly-ADP Ribose Polymerase) is a gene that repairs damage to DNA. In healthy cells this is an essential gene in preventing any lasting DNA damage (mutation) that may cause cancer. However, in cancer PARP can work against treatments like radiotherapy and chemotherapy. In Radio- and chemotherapy, the radiation and drugs deliberately damage the DNA to kill the cancer cells and stop them from dividing. PARP can mend this deliberate damage, thereby stopping the anti-cancer therapy from working. PARP inhibitors are a new class of drugs that stop PARP from working against anti-cancer therapies in this way, and have shown some fantastic results in trials against other cancer types. This project will investigate whether Ewing's sarcoma cells in the laboratory are susceptible to one PARP inhibitor drug (called AG-014699) when co-treated with radiation or chemotherapy drugs.

Outcomes from the research
The PARP inhibitor AG-014699 increased the killing-potential of both radiation and the chemotherapy drug camptothecin in Ewing's sarcoma cells. More DNA damage was seen in cells treated with AG-014699, showing that it was successfully preventing DNA repair. This is a good indication that these new drugs might be useful in the clinic in combination with standard therapy.

Following on from this positive data in cells, a clinical trial is being planned to test this drug combination in Ewing's sarcoma patients.

Dr Teresa Coughlan, Research Associate at the University of Sheffield
BCRT research grant 18
Pump priming Targeting gene therapy to bone cancers using novel delivery of RNA £48,199
 

Aims of the research
One of the challenges of treating cancer is how to target tumour cells without damaging healthy tissue. One technique that is being developed to achieve this is the use of bacteria to target tumour cells. The centre of a tumour is low in oxygen and contains many dead and dying cells. This makes is exactly the environment that many bacteria live in, and so bacteria colonise (live in) tumours preferentially over healthy parts of the body. In this laboratory project Dr Coughlan will use salmonella bacteria, which have been genetically attenuated - which means that their harmful genes have been removed so that the bacteria can't make people sick. The attenuated salmonella will carry an anti-tumour gene, in the form of RNA (gene message) into cancer cells to try to find a new way to kill cancer cells.

Outcomes from the research
This project was filled with technically challenging stages, which were not all achieved in the short time-scale of this project. Despite proving the infection of other cancer cells was possible with the attenuated bacteria, the osteosarcoma cells that were tested appeared to be resistant to infection, and so the effects in osteosarcoma could not be measured. The gene that was altered in the osteosarcoma cells caused cells the cells to grow so slowly that it was difficult to analyse them. This highlights how difficult this kind of cutting edge research can be. In the future Dr Coughlan would like to try this work again but using a different kind of bacteria, which the osteosarcoma cells might be more susceptible to.

Dr Britta Vormoor Honorary Clinical Lecturer at Newcastle University
BCRT research grant 20
Pump priming Investigation of DNA-PK inhibitors as chemo- and radio-potentiating agents in Ewing's sarcoma £29,820
 

Aims of the research
DNA-PK is a gene that repairs the DNA damage caused by chemotherapy and radiotherapy, which prevents these therapies from killing cancer cells. Drugs are being developed to target and switch off DNA-PK in cancer, and one of these drugs is called NU7441. NU7441 has not yet been tested in Ewing's sarcoma and so this project aims to use Ewing's sarcoma cells in the laboratory to see whether NU7441, in combination with radiation or chemotherapy, is effective Ewing's sarcoma cells and whether the addition of NU7441 increases the anti-cancer qualities of chemo and radiotherapy.

Outcomes from the research
This project is still on-going.

Ms Susie Pearce, Health Service Researcher for Young People with Cancer at University College London Hospital
BCRT research grant 21
Project grant Teenagers and young adults with bone sarcomas: Patient and professional perception of participation in clinical trials £29,893
 

Aims of the research
Clinical trials are a crucial part of how new drugs and treatments are developed. Clinical trials rely on patients volunteering to take part, and for a clinical trial to give the most informative results the trial needs to have as many patients as possible. Trials around the world have struggled to recruit enough teenagers and young adults, and in this research project Ms Pearce seeks to identify the reasons behind this. To achieve this, patients and healthcare professionals will be interviewed to ask why young people with bone sarcomas choose to either decline or accept invitations to participate in clinical trials. Also healthcare professionals will be asked how they go about asking young patients to take part in clinical trials. From this information it is hoped that the researchers can identify any factors that encourage teenagers and young adults to take part in clinical trials and feed that information back to healthcare professionals and research groups who run trials.

Outcomes from the research
During the course of this project the researchers spoke to 21 teenage and young-adult bone cancer patients, and 18 healthcare professionals. These participants were interviewed by the researchers about their experience of being asked to join/asking patients to join clinical trials.

Among the key factors in the patient's perspective were whether the patient found making the decision to join a clinical trial to be a pressure, and a decision that had to be made very quickly after being diagnosed. Having a sense of being in control of that decision was very important, as was having good communication with the medical professionals. The professionals who were interviewed in this study showed a good understanding of the perspectives of their young patients and had age-appropriate strategies to communicate clinical trial information to patients.

The researchers hope that this study can contribute to the understanding of how teenagers and young adults decide whether to take part in a clinical trial. The researchers hope to use the information gained in this study to advise future designers of clinical trials.

Presentations and publications from this research:

  • Papers in preparation
    Pearce S, Brownsdon A, Lavender V, Fern L, Gibson F, Whelan J Participation in clinical trials: the perceptions of young people with sarcoma and health professionals. A qualitative study. Qualitative Health Research

  • Peer reviewed posters/presentations
    Pearce S, Browndson A, Lavender V, Fern L, Gibson F, Whelan J (2012)Participation in clinical trials: perceptions of young people with sarcoma and the professionals who look after them. Poster at the National Cancer Research Institute Conference, Liverpool. 6th November 2012

  • Invited posters/presentations
    Pearce S, Brownsdon A, Lavender V, Gibson F, Fern L, Whelan J (2012) Participation in clinical trials, perceptions of young people with sarcoma and the professionals who look after them. A study in progress. Poster at the Bone Cancer Research Trust Conference Oxford 23rd June 2012

    Lavender V (2012) "What do young people with bone cancer and the health professionals that look after them think about participating in clinical trials?" presentation at the Bone Cancer Research Trust Conference Oxford 23rd June 2012

    Fern L and Brownsdon A (2012) The Critical importance of clinical trials. Teenage Cancer Trust International Conference London 25th June, 2012.

    Browndson A Teenagers and young adults with bone sarcomas: patient and professional perceptions of participation in clinical trials PANCARE London, 8th October 2012

  • Local presentations
    Pearce S Presentation to the Children and Young Peoples Cancer Service October 2011 and October 2012 UCLH

    Brownsdon A Presentation to the London Sarcoma Group, September 2012
    Pearce S Presentation to the National Cancer Research Institute Teenage and Young People Clinical Studies Group November 2012

Dr Sarah Welsh, Academic Clinical Fellow at University College London Hospital
BCRT research grant 22
Pump priming Validation of HIF1a as a drug target in chondrosarcoma and osteosarcoma £9,949
 

Aims of the research
HIF1a (Hypoxia Inducible Factor 1a) is a gene that is switched on in cancer cells that are growing in the low-oxygen environment inside a tumour. HIF1a is a controller gene that switches on many genes to make the tumour cells more able to grow in that environment, and also to protect the tumour from chemotherapy. In this project, Dr Welsh will investigate whether targeting and silencing HIF1a in chondrosarcoma or osteosarcoma cells could provide a new basis for treatment of these primary bone cancers. Osteosarcoma and chondrosarcoma cells will be grown in the laboratory in normal and low oxygen conditions. HIF1a will be switched off and changes in cell growth, cell death and changes to HIF1a-controlled genes will be measured.

Outcomes from the research
As can often happen in research, another research group were already working on a project very similar to this, and published their results around the time that Dr Welsh started this work. Therefore in order to not waste research money by duplicating the same experiments, Dr Welsh and her colleagues modified the project slightly. Instead of silencing the HIF1a gene using a technique called RNAi (which was the original plan) the researchers used a new, experimental drug to switch HIF1a off instead.

The results showed that the new drug was effective at switching off HIF1a in osteosarcoma and Ewing's sarcoma cells grown in the laboratory. Also, the drug was able to stop the osteosarcoma and Ewing's sarcoma cells growing; and the drug had a stronger effect on these primary bone cancer cells then on other cancer cell types. The researchers plan to continue experiments to see whether this drug could be suitable for osteosarcoma and Ewing's sarcoma patients.

Presentations:
Young Investigators presentation: The Connective Tissue Oncology Society annual meeting, Chicago October 2011.

Mr Lee Jeys, Consultant Orthopaedic Surgeon at the Royal Orthopaedic Hospital in Birmingham
BCRT research grant 26
Project Can functional MR based imaging reliably predict the pre-operative response to chemotherapy in osteosarcoma patients under the age of 21 years? £60,000
 

Aims of the research
The more detailed information a surgeon has about a bone tumour, the more effectively the tumour can be removed with minimal loss of healthy, surrounding bone. New 'functional imaging' techniques can use MRI scanning to detect qualities in the tumour such as cellular structures, metabolite profiles, and the levels of oxygen inside the tumour, which all give an indication of how well the prior chemotherapy has worked. This project will test this kind of imaging on primary bone cancer patients under the age of 21 and before their surgery, and the results compared to what is really seen inside the tumour after it has been removed. This will test whether the imaging is an effective tool in providing better information about primary bone tumours, to enable informed surgical decisions to be made.

Outcomes from the research
This project is still on-going.

BCRT research grant 35
Pump-priming Can we reliably detect viable, dying, or dead Ewing’s sarcoma cells in peri-tumoural tissue following induction chemotherapy £30,000
 

Aims of the research
When a surgeon operates to remove a Ewing’s sarcoma tumour, the aim is to remove the whole of the tumour, plus a thin layer of healthy tissue, to make sure that every cancer cell is removed. Sometimes however, despite the surgeon’s best efforts, the Ewing’s sarcoma grows back. This is called a ‘local recurrence’. The aim of this study is to find out whether the reason for these local recurrences is that cancer cells from the tumour can escape into the surrounding healthy tissue, where they hide for some time before growing back later. In this research study, during the surgery for remove Ewing’s sarcoma, small samples of the healthy muscle surrounding the tumour will be taken, to check to see whether cancer cells can be detected.

This information will help to identify which patients need to have radiotherapy after surgery, in order to make sure that all of the cancer cells are killed.

Outcomes from the research
This information will be updated when the project has finished.

Professor Farida Latif, Professor of Human Molecular Genetics at the University o Birmingham
BCRT research grant 27
Pump priming Epigenetics of Ewing's sarcoma and Ras Association Domain Family of genes £29,916
 

Aims of the research
Inside cells, the DNA that forms genes is stowed away neatly so that it doesn't interfere with the normal processes inside the cell. The DNA is wrapped around structures called histones, which are like cotton-reels. If a gene is wrapped tightly around a histone then it can't be read by the cell, so the gene is switched off. This is known as 'epigenetic regulation', and genes can be switched off in this way, or released to be switched on, rapidly in response to signals inside the cell. In cancer, many genes undergo changes in their epigenetic regulation and this contributes to the progression of cancer. The RASSF family of related genes is an anti-cancer gene that is epigenetically switched off in cancer, including in the majority of Ewing's sarcoma samples tested. This project will investigate what role RASSF genes play in Ewing's sarcoma.

Outcomes from the research
This project is still on-going.

BCRT research grant 28
Small grant Epigenetics of chordoma £9,900
 

Aims of the research
Professor Latif's research group applied for this funding to extend their research into the epigenetic regulation of the RASSF family of genes (as described in her previous grant) into chordoma samples.

Chordoma is a very rare primary bone tumour of the spine, which is diagnosed in around 25 people in the UK and Ireland each year. This tumour is so rare that very little is known about the genes that cause chordoma and drive its growth. Chordoma starts from a type of cell in the spine, which is known as a 'notochord cell'. This project will identify whether the RASSF family of genes could be involved with this kind of bone cancer.

Outcomes from the research
This project is still on-going.

Dr Sandra Strauss, Senior Lecturer and Consultant Medical Oncologist, University College London Cancer Institute
BCRT research grant 33
Project grant Investigation of CL67 as a first-in-class novel inhibitor of the HIF1a pathway in osteosarcoma £74,797
 

Aims of the research
This research project follows on from the work done by Dr Sarah Welsh and Dr Sandra Straus in BCRT project number 22. This previous project identified that a new potential new drug, called CL67 is effective at killing osteosarcoma cells. This new project will work out in more detail whether CL67 is suitable to be used as a treatment for osteosarcoma patients.

CL67 targets a gene called HIF1a. HIF1a is a gene that gets switched on in the cancer cells inside a tumour, where there is a poor blood supply and therefore very little oxygen reaching the cells. HIF1a acts to switch on an array of other genes that help the tumour cells to survive in this challenging condition. If HIF1a can be targeted and shut down, then more of the cells inside a tumour will be more sensitive to chemotherapy and radiotherapy, making the cancer easier to treat.

Outcomes from the research
This information will be updated when the project has finished.

Dr Neil Cross, Senior Lecturer, Biomedical Research Centre, Sheffield Hallam University
BCRT research grant 34
Pump-priming Enhancement of Nuclear Death Receptor sensitivity in osteosarcoma using Nuclear Export Inhibitors £29,419
 

Aims of the research
A new kind of anti-cancer drug, called TRAIL, has been developed in recent years. TRAIL is very promising because it can kill cancer cells without harming healthy cells. However, cancer cells can quickly find ways to defend themselves against TRAIL – this self-defence is called ‘resistance’.

In this research project Dr Cross and his team will try out a new way to stop osteosarcoma cells from becoming resistant to TRAIL. The research will examine whether treating osteosarcoma cells with TRAIL in combination with another drug, leptomycin, will overcome the cancer cells’ resistance to TRAIL.

Outcomes from the research
This information will be updated when the project has finished.

Dr Kenneth Rankin, Academic Clinical Lecturer in Orthopaedic Surgery, University of Newcastle
BCRT research grant 37
Small grant The feasibility of detection and characterisation of circulating tumour cells in osteosarcoma £9,993.41
 

Aims of the research

Osteosarcoma is the most common form of primary bone cancer in children, teenagers and young adults and the survival rates for this cancer have not improved over the last 30 years.

One of the barriers to improving the survival rate of osteosarcoma is thought to be that patients often struggle to get a correct diagnosis and that the process of getting diagnosed is slow. The faster a patient can be diagnosed, the faster they can start treatment and it is believed that this leads to better outcomes for the patients.

At present there is no simple blood test that can confirm a diagnosis of osteosarcoma; instead patients need to be referred for X-rays and biopsy of the tumour. In contrast, for some cancers there are tests that can look in the patient’s blood and detect low levels of cancer cells in the blood. These cells are known as ‘Circulating Tumour Cells’ or ‘CTCs’ and tests for CTCs in breast cancer, prostate cancer and colon cancer are becoming established as methods for detecting cancer at an early stage.

This project aims to find out the best way of detecting CTCs in osteosarcoma patients. This kind of a test would not only help in detecting osteosarcoma early, but might be able to help show how well

Outcomes from the research
This information will be updated when the project has finished.

Last updated: 25.07.2013