Cancer is caused by mutations (or mistakes) in DNA – a person’s biological instruction manual. Some of these mutations are specific for certain cancer types and are therefore useful to make specific diagnoses and in some instances to determine the likelihood of a cancer becoming more aggressive in behaviour. There have been recent studies, albeit in small sample numbers that have discovered a spectrum of specific mutations in a rare form of cancer called malignant peripheral nerve sheath tumours (MPNSTs).
Sarcomas are difficult to treat and there is an urgent need to develop more effective therapies. Like other cancers, sarcomas, develop blood vessels that ‘feed’ them with oxygen and nutrients, and allow their growth and spread. Several drugs have been developed that specifically target and damage these blood vessels and some of these drugs are now being used to treat sarcoma. While some patients clearly benefit from this type of therapy others don’t, making it difficult to tailor treatments to the needs of individual patients.
Rhabdomyosarcoma is a devastating muscle cancer that occurs in infants and children. In our previous work that was part funded by Sarcoma UK we have shown that a protein termed YAP is present and active in this type of cancer. When we artificially activate YAP in mouse muscle stem cells, all mice developed rhabdomyosarcoma. Additionally, when we reduced YAP levels in human rhabdomyosarcoma cells then they switched from cancer cells into cells that resemble normal muscle.
Sarcomas are rare tumours that account for approximately 1% of all cancers in the UK. They represent a challenge to treating clinicians as diagnosis is often delayed and the tumours are commonly in an advanced stage or have spread to other parts of the body. Current treatment approaches for these advanced tumours have shown only modest response rates of 12-24% and are associated with significant toxicity in patients.
This proposal aims to develop new bioactive materials to improve clinical outcomes for patients suffering from bone sarcoma. The developed materials will provide a control release of key metal ions to induce tumour cell death and simultaneously stimulate grow new bone. In addition the material will contain natural antibacterial agents to reduce the probability of surgical site infections. Furthermore we envisage that the material will enhance blood flow therefore significantly reducing patient healing times.
This study looks at the quality of life of patients being treated for advanced sarcoma. Prospective means it looks at patients as they go along, which gives stronger data. This is better than retrospective data which looks at events in the past where memory or uncertainty often makes the information unreliable.
People with locally advanced or sarcoma that has spread or whose sarcoma has have had recurred after surgery may only be eligible for palliative treatment so quality of life becomes the primary concern rather than defeating the sarcoma.
Deaths from cancer in children are, thankfully, rare. However, a leading cause of cancer related deaths in children is rhabdomyosarcoma, a soft tissue sarcoma. More effective treatments are urgently required and Dr Shipley proposed that increased understanding of the underlying molecular mechanisms in development and spread of rhabdomyosarcoma would yield new angles for investigation.
This is an example of a translational research project, looking at ways to transfer results from the laboratory into a clinical trial in patients in a Phase 1 Trial. They are developing a system for treating limb sarcomas using Isolated Limb Perfusion (ILP) as well as oncolyic virotherapy (anti-cancer viruses)
This is a basic science project, finding out more about how chromosome abnormalities in the nuclei of sarcoma cells might upset the regulation of cell turnover. If they can understand more about this it might be an opening to developing new approaches to treatment.