University of Southampton
This project uses new cutting edge techniques to compare rhabdomyosarcoma cells which do and don’t respond to chemotherapy. By understanding how some cells resist chemotherapy, we can work towards making them responsive to treatment.
Linking cellular heterogeneity to therapeutic response in rhabdomyosarcomas
Rhabdomyosarcoma is the most common type of soft tissue sarcoma to occur in childhood, with up to 70 new cases in the UK each year. Most children with tumours at a single site in the body respond well to treatment, with a 5-year survival rate of 70%. However, patients with tumours that have spread throughout the body, or patients with residual disease in unfavourable sites have lower survival rates, and there has been little improvement in survival over the last few decades despite an increase in treatment intensity.
To improve patient outcomes we need to determine how specific rhabdomyosarcoma tumour cells resist treatment and develop new therapies which target these resistant cells. To achieve this we will first identify tumour cells which respond differently to treatment, by isolating single rhabdomyosarcoma cells, cloning them and testing the clone cells response to standard chemotherapy.
Using new cutting edge techniques we will characterise gene expression and DNA sequence changes in the most sensitive and resistant cells. We will identify a list of key genetic differences associated with chemotherapy response by comparing the responsive and resistant cells.
The key factors we identify which enable cancer cells to escape therapy can then be applied to patient samples to better understand resistance and disease recurrence. Furthermore, the clone cells that we will generate can be used to test other drugs that may be more effective than standard treatments in eliminating these chemo-resistant cells. This project has the potential to improve overall outcome and quality of life for rhabdomyosarcoma patients.