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PROJECTS 1 & 2 - UNIVERSITY OF SHEFFIELD - 

It is shocking to note that chemotherapy treatment for osteosarcoma hasn’t changed in the past 30 years and doesn’t work in all cases. New ways to fight this devastating disease are clearly needed. As a result of funding from Willberry's Research, a team comprising a Post-Doctoral Researcher (Luke) and a PhD Student (Victoria), led by Prof Allie Gartland, is testing over 5,000 existing drugs and compounds to assess their effect in killing osteosarcoma cells. The team hopes to identify potentially useful new drugs and pathways to develop new more effective treatments to improve patient responses. Because the drugs being screened have already been approved for human use, the identification of new drug candidates could potentially be very rapid and reach the clinic in a much shorter time as a result.

Post-doctoral researcher: Luke Tattersall

Supervisors: Professor Alison Gartland and Professor Dominique Heymann

Dates:  January 2019 - December 2023

 

 

 

 

 

 

 Photo: Luke Tattersall

The main current therapeutic approach for osteosarcoma is a combination of methotrexate, docorubicin, cisplatin, and/or ifosfamide associated with surgery. Unfortunately, not all patients respond to these chemotherapy drugs, as their tumour becomes ‘chemo-resistant’ and their overall 5-year survival rate is drastically reduced. The need for alternative, more effective treatments to increase the survival rates of osteosarcoma patients is clear.  The scientific team being funded by Willberry's Research is using ‘High throughput screening’ (or HTS) of compound ‘libraries’ to identify whether existing drugs can be used in osteosarcoma. Commercially available libraries will be used to enable the screening of over 5,000 drugs and compounds in vitro. Top hits will be validated in pre-clinical models of osteosarcoma. This would provide a substantial opportunity to identify new drug candidates for rapid clinic/patient benefit, as these compounds have already been approved for human use.

PhD student: Victoria Tippett

Supervisors: Professor Alison Gartland and Professor Dominique Heymann

Dates:  October 2019 - March 2023

Victoria is also working on this larger project, which aims to tackle chemotherapy resistant osteosarcoma. This involves developing a model of chemotherapy resistance, so that she can later screen over 5,000 drugs. From this, her group aims to better understand why osteosarcoma becomes resistant to treatment and find new drugs that could benefit these patients.  

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PROJECT 3 - UNIVERSITY OF SOUTHAMPTON

PhD student: Hannah Smith

Supervisors: Dr Stephen Beers, Dr Janos Kanczler and Dr Juliet Gray

Dates: January 2019 - January 2022 

Osteosarcoma is the most common bone sarcoma in adolescents and has a poor outlook. Novel treatments for this poorly met patient group are clearly needed but their development is hampered by the complexity of the disease and the environment in which it grows. Stephen Beers, Janos Kanczler and Juliet Gray are a team of bone and cancer specialists brought together by funding from Willberry’s Research.  Hannah is developing 3D models of osteosarcoma to gain a better understanding of the interactions between the osteosarcoma tumour and its surrounding environment. Osteosarcoma is an incredibly complex type of cancer and currently very little is known about the environment in which it grows. With more knowledge, investigations into more effective treatments for osteosarcoma will be possible, improving patient responses.

This project undertaken at the University of Southampton is focusing initially on the drug mifamurtide (also known as Mepact) which is used in patients, but to which not all respond, to understand how this drug works and potentially how to make it work better in more patients.

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PROJECT 4 - UNIVERSITY OF MANCHESTER

PhD student: Alex Dzhoneva

Supervisors: Katie Finegan, Kaye Williams, Adam McMahon

Dates: October 2019 – January 2023 

 

 

 

 

 

 

 

 

Photo: Alex Dzhoneva

Previous work performed in this lab has found that a protein called ERK5 can promote the progression of osteosarcoma. It has also been found that high levels of the ERK5 protein can increase the chances of chemotherapy resistance and the spread of osteosarcoma around the body. Therefore, higher levels of ERK5 are linked to a reduced chance of survival in patients. Initial evidence has found that, by removing ERK5, tumour cells and immune cells are no longer able to communicate with each other. This is really positive data from this lab group as it is the communication between the tumour cells and the immune cells which allows the cancer to spread around the body. It is currently unknown how this happens, but removing ERK5 has shown to stop the spread of cancer to the lungs in models of the disease which have been used in the lab. It is really important to fully understand how this happens in order to effectively treat osteosarcoma and to develop this treatment for patient use in the future. This project aims to find out exactly how ERK5 works in the progression of osteosarcoma and determine whether removing ERK5 can improve the response to chemotherapy. This is a promising new avenue for the treatment of osteosarcoma.

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PROJECT 5 - UNIVERSITY OF SOUTHAMPTON

PhD student: Belle Creith

Supervisors: Dr Claire Clarkin, Richard Oreffo, Sumeet Mahajan

Dates: October 2019 – October 2022 

 

 

 

 

 

 

Photo: Belle Creith

Belle aims to look for osteosarcoma-specific characteristics that may be targeted therapeutically and then develop methods for early detection of osteosarcoma, something which is currently lacking. To do this, she is using Raman spectroscopy which is a highly sensitive laser technique that will define the chemical fingerprint of osteosarcoma cells, comparing them to healthy bone cells. It is hoped that there will be key molecular differences between the osteosarcoma cancerous cells and the healthy bone cells which may help to suggest targets for future therapeutic treatments. It is well understood that tumours need blood vessels to grow and spread around the body and therefore Belle is also interested in investigating how osteosarcoma-specific traits may affect the many blood vessels within cancerous bone. It is believed that Raman Spectroscopy has the potential to be developed into a tool which could be used by the Medical Health Services to allow for the early enhanced diagnosis of bone cancer which is so important in the fight against osteosarcoma.

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PROJECT 6 – Middlesex University

PhD student: Daniela Paternina

Supervisors: Dr Helen Roberts (Middlesex University) and Dr Scott Roberts (Royal Veterinary College)

Dates: April 2021 – March 2024

Preclinical and clinical evidence highlight that osteosarcoma tumours likely reside in the bone environment due to ‘protective’ interactions with bone cells. It is hypothesised that disruption of these protective interactions causes the tumour to move from the bone to the lungs in a process called metastasis. In this project, a Willberry’s Research-funded PhD student, Daniela Paternina, will investigate why osteosarcoma tumours metastasise to the lungs. Along with our collaborators at the Royal Veterinary College (Dr Scott Roberts; Senior Lecturer in Translational Skeletal Research), Daniela will use cutting edge cell-based assays to define the role of bone cells and the lung environment, with the aim of identifying drug targets that specifically supress tumour metastasis.

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PROJECT 7 – Kings College London

PhD student: Michael Dack

Supervisors: Professor Agamemnon Grigoriadis (Kings College London)

Dates: October 2022 – September 2025

      Photo: Michael Dack

Michael is looking at stopping the growth of bone tumours in their tracks, with the help of SnMP, which is already an approved drug used for neonatal jaundice. Research using drugs that are already FDA-approved has massive benefits, as it means that, if successful, going from bench to bedside – and actually being able to use the drug to treat a real patient – is much, much quicker.

 Thank you to everyone who has made this possible