Lead investigator: Prof Janet Shipley, The Institute for Cancer Research
Funded by The Little Princess Trust and administered by CCLG
Funded December 2017
Award: £98,329.00
Rhabdomyosarcomas are rare types of cancer but a major cause of death from cancer in children. New and less toxic treatments are urgently required to improve patient outcomes.
A new international clinical trial for rhabdomyosarcoma patients is being administered from the UK and will open in 2018. This trial has been designed with the opportunity to treat high-risk patients with new drugs in combination with standard treatment.
The aim of this study is to identify new drugs using novel 3-dimensional models that we recently established from tumours of high-risk patients. These models better represent patients’ tumours than widely used cell lines grown in 2-dimensions for many years. They are suitable for small scale screening of drugs, based on our pilot data, and more cost effective than using mouse models.
The study aims to select drugs that target abnormal DNA repair processes in rhabdomyosarcoma cells. This will enhance the usual DNA-damaging effects of the standard treatment and make it more effective. This sensitisation may ultimately enable decreasing doses of toxic drugs to reduce side-effects.
This method enables the research team to test drugs at clinically-relevant doses, which isn’t possible with most current screening strategies.
The 3D models, plus normal control cell cultures, will be assessed during and after different drug treatments, alone and in combination, over a 3 week timeframe. The team will use digital analyses of growth and quantification of cell death to determine the extent of any enhancing effects of adding new drugs.
Results will enable drugs to be prioritised for subsequent pre-clinical testing. This will support inclusion of new drugs into the trial for rhabdomyosarcoma patients with the expectation of improving their outcome.