Research Fellowship grants awarded

In November 2012, BCRT awarded its first Research Fellowship grants. These grants will each pay for a clinician or scientist to undertake a two or three year research project that will aim to improve the outcomes of primary bone cancer patients. The researcher will write up their project and submit it to their University to be examined for an MD (for clinicians) or PhD (for scientists) qualification. These qualifications provide scientific training to allow the recipient become a leading bone cancer researcher of the future.

These fellowship projects are BCRT's latest step in investing in the bone cancer research community, by providing funding for the training of a new generation of bone cancer researchers in the UK and Ireland.

One research fellowship was awarded in 2014, pushing BCRT's total research grant spend to over £1,700,000.00

not yet appointed
Prof Salter, Prof Brunton, Dr Langdon, Prof Hupp & Dr Hayward 'NG2/CSPG4 in Osteosarcoma : functional roles and novel therapeutic target' £114,018 over 3 years for PhD qualification

This study is looking at a molecule called NG2/CSPG4 and how this may be used as a therapeutic target for osteosarcoma.

NG2/CSPG4 correlates with tumour growth, tumour spread, aggressive behaviour and poor outcome in other cancer and can influence how effective drugs are at killing cancer. This molecule is also found in tumour cells of osteosarcoma patients.

The first part of this project involves genetically modifying osteosarcoma cells causing them to either lose or overproduce NG2/CSPG4. They will then investigate how this influences cell growth and spread.

The second part of the study is to investigate novel treatments that may inhibit the function of NG2/CSPG4 by assessing whether antibodies against NG2/CSPG4 are able to reach and bind to growing osteosarcoma cells.

These studies will support future development of anti-NG2/CSPG4 therapies for osteosarcoma which would either inhibit the detrimental effects of NG2/CSPG4 on osteosarcoma cells or be used to specifically deliver toxins or radioactive molecules to osteosarcomas and thereby kill the cancer cells with limited effects on normal tissues.

Three research fellowships were awarded in 2012, pushing BCRT's total research grant spend over the £1,000,000.00 barrier!

The projects that were selected for funding reflect three important areas of bone cancer research: genetics, radiotherapy and new drug development. These projects will lead to a better understanding of the treatment of osteosarcoma, Ewing's sarcoma, chondrosarcoma and chordoma. BCRT is thrilled to introduce our new Research Fellowship projects:

Dr Harriet Holme, University College London Hospital, London
Dr Sandra Strauss and Professor Adrienne Flanagan, University College London Hospital, London 'Identifying biological dependencies in osteosarcoma to develop novel therapeutics' £225,000 over three years for PhD qualification

This project is a comprehensive study to identify which genes drive the growth of osteosarcoma tumours. These genes can be used as targets for future research to design new drugs and therapies to combat osteosarcoma.

The project uses a two-stranded approach to identifying which genes are essential for keeping osteosarcoma cells alive and letting them grow. Fifteen different osteosarcoma cell lines will be used in the experiments to ensure that the results are not just relevant in one kind of osteosarcoma tumour. Firstly, an 'siRNA screen' will be used. siRNA is a gene silencer, which can be targeted very specifically to just one gene at a time. siRNA will be used to silence 700 genes one by one, in all fifteen cell lines, in order to identify which genes are essential for the continued growth of the osteosarcoma cells.

The second stage of the project is even more complex. In order to back-up the study using siRNAs, a library of compounds will be screened. This library contains 400 drugs that each target and shut-down different genes in the cells. Computer analysis of both stages of this project will then show the most powerful genes and gene-networks that could be targeted for the treatment of osteosarcoma. Any such genes can be examined in 80 more osteosarcoma tumour samples, to see whether these genes are switched on in many osteosarcoma tumours.

Dr Harriet Holme will be carrying out this research and will submit this for a PhD qualification.

After completing undergraduate training at Cambridge and University College London, Harriet has undertaken paediatric training in London. Harriet was an Academic Clinical Fellow at the Blizard Institute, London, and appointed to national subspecialty training in paediatric oncology in September 2012. Harriet has a strong interest in academic paediatric oncology, particularly with regards bone tumours. Harriet believes this project is an exciting opportunity to identify potential novel therapeutic targets for the treatment of osteosarcoma and is looking forward to collaboration with the BCRT.

Harriet has already achieved a lot in her career and has received a world-class medical training which has led her to an interest in childhood cancers and bone cancer research in particular. We are very excited to see what Harriet will achieve during this project.

Not yet appointed
Professor Nicholas Athanasou, Nuffield Orthopaedic Centre, Oxford 'Analysis of osteolysis in Ewing's sarcoma and osteosarcoma and the effect of resorption inhibitors on tumour growth' £70,100 over three years for PhD qualification, co-funded with Sarcoma UK

This project, which is the first research grant to be joint-funded by BCRT and Sarcoma UK, aims to find out whether some drugs that are already prescribed for osteoporosis could be useful in Ewing's sarcoma and osteosarcoma.

These drugs, resorption inhibitors, work by stopping the action of a type of bone cell called an osteoclast. In healthy bone, osteoclasts break down and re-sorb tiny areas of damaged bone so that new bone can be made to replace it, by bone-building osteoblast cells. This means that the balance between osteoclast and osteoblast activity is vital. Too much osteoclast activity causes thin, fragile bones (osteoporosis) and too much bone creation causes brittle and disfigured bones (osteopetrosis).

Osteoclasts are also involved in the progression of Ewing's sarcoma and osteosarcoma. The osteoclast cells are not a part of the tumour, but are activated by the tumour cells. This activation causes the osteoclasts to break down the healthy bone that surrounds the tumour, thus allowing the tumour to grow bigger and spread outside the bone.

Resorption inhibitors are used in the treatment of osteoporosis, to halt the action of osteoclasts, to prevent the bones from being broken down. This project will investigate whether resorption inhibitors are also suitable for stopping the activation of osteoclasts in primary bone cancers.

Dr Franél le Grange, University College London Hospital, London
Dr Beatrice Seddon 'How outcomes for patients with bone sarcomas can be improved by intensity modulated radiotherapy and proton radiotherapy: Optimising delivery, efficacy and toxicity profiles' £128,048 over two years for MD qualification

One of the most important recent developments for UK and Ireland cancer patients in the last year has been the UK government's commitment to building two new proton therapy centres in the UK, one in London and one in Manchester, to open in 2017. This project aims to find the best ways to treat primary bone cancer patients using proton therapy and Intensity Modulated Radiation Therapy (IMRT).

Radiotherapy is a powerful tool that can be used to treat certain kinds of cancer. One drawback to this is that it can be hard to reach tumours without also exposing the surrounding healthy tissues to radiation. This radiation can cause damage to these healthy tissues, causing long-term health problems. Two new types of radiotherapy that can overcome this problem are proton therapy and Intensity Modulated Radiation Therapy (IMRT).

Proton therapy uses very high energy beams that can be focussed precisely into the tumour and have very little effect on the surrounding tissues. This means great tumour-killing power with lesser side-effects. IMRT is a way of focussing radiotherapy beams into the precise 3D shape of a tumour, and this more precise focussing means that the healthy tissues can be avoided. Both of these techniques are very new and so this project will identify which tumours will be best treated with which type of radiotherapy.

This research will be carried out by Dr Franel le Grange, who introduces herself here:

'I trained as a clinical oncologist in Cape Town in South Africa. I moved to London in 2008 and I have been working with the team at the London Sarcoma Service and University College Hospital for the last 3 years, specialising in sarcoma treatment. I am currently working as a clinical research fellow. The focus of my research is improving radiotherapy treatment and outcomes for patients with sarcoma. I am very excited to be working with the BCRT on an exciting research project that will look at how we can use advanced radiotherapy techniques, including Intensity Modulated Radiotherapy and Proton beam radiotherapy, to treat bone sarcomas. This work is extremely important as we lead up to the opening of two Proton beam treatment centres in the UK in 2017.'