Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Sally George, Institute of Cancer Research
Award: £ 244,204.00
Awarded March 2023
Neuroblastoma is thought to start whilst the baby is still in the womb, in early versions of the cells that will eventually become nerve cells. This is one of the reasons why neuroblastoma is so aggressive – these very early cells aren’t locked in to any one type of cell or function yet, meaning that they still are still able to adapt and change.
Like other cancers, neuroblastoma cells grow out of control, ignoring the normal ‘rules’ for healthy cells that only let them multiply a certain number of times. In order for neuroblastoma cells to multiply, they need to maintain an important part of their genetic code – the telomeres. Telomeres are bits of DNA that protect the ends of the chromosomes (which hold each cell’s genetic code). In normal cells, telomeres get shorter every time a cell divides until there is not enough left for another successful division. This stops cells from growing out of control.
Cancer cells use a few different ways to keep their telomeres long so they can continue to grow. A quarter of neuroblastoma tumours use a method called ALT (alternative lengthening of telomeres) that sticks extra bits of DNA to the telomeres, keeping them long. Neuroblastoma with ALT is especially hard to treat and often doesn’t respond to chemotherapy.
In this project, Dr Sally George at the Institute of Cancer Research is making cancer models that behave like neuroblastoma with ALT. Her team will use these to learn why ALT cells are so resistant to chemotherapy.
To mimic the cells which neuroblastoma starts in, Dr George’s team will turn stem cells into early nerve cells before making them develop ALT. This will show the researchers how ALT changes the behaviour of early nerve cells, which they hope will increase their understanding the cause of neuroblastoma. The researchers will also look at how early nerve cells with and without ALT respond differently to chemotherapy drugs, to understand the reason why ALT neuroblastoma is so hard to treat.