Patients with inoperable or metastatic soft tissue sarcoma have a poor prognosis with overall survival rates (of approximately a year) when treated with current first line palliative chemotherapy. There has been no change in the standard of care for over 20 years. Improved outcomes could be achieved by identifying biomarkers that can select soft tissue sarcoma patients most likely to benefit from current and novel therapies.
Myxofibrosarcomas are cancers that most commonly develop in the limbs. Surgery is the main treatment but because of the way these cancers grow, it is a challenge to successfully remove them. Unlike other cancers that are easily visible to the surgeon, myxofibrosarcomas often infiltrate nearby tissues making it difficult to accurately assess how much cancer is present. There is a risk that some cancer is left behind after surgery, and this may result in a poorer outcome for the patient.
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.
Magnetic nanoparticles will produce heat if exposed to an alternating magnetic field. If magnetic nanoparticles can get inside a tumour, an alternating magnetic field can be applied so that the particles heat up and the tumour cells are killed. This project investigated two different ways to deliver nanoparticles into the tumour using mesenchymal stem cells. One worked, one didn’t, and the group has now secured future funding to keep investigating the method that proved successful.
Rhabdomyosarcoma is a muscle cancer that occurs in children. Previous research has shown that activation of a protein called YAP is a key cause of rhabdomyosarcoma, however how activation occurs is still unknown. This project is investigating how activation of YAP happens, and also if the protein has the potential to be used as a drug target. If we can understand how YAP turns on, we can work out how to turn it off.
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.
This project is using DNA sequencing technology to identify the genes which make rhabdomyosarcoma a particularly aggressive cancer. Alongside this, the project will look for genes which could be potential drug targets in the treatment of rhabdomyosarcoma.