Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Alejandra Bruna, The Institute of Cancer Research
Award: £61,256.00
Awarded July 2024
Childhood cancer is a leading cause of disease-related death for children. One of the problems is cancer that doesn’t respond to treatment and then relapses. This is very challenging to treat. Some cancers, like neuroblastoma, are especially good at adapting to treatment.
Dr Alejandra Bruna’s lab at The Institute of Cancer Research has found that neuroblastoma has an unusual way of surviving treatment. Whilst most cancer cell behaviour is thought to be based on hard-coded genetic changes, Dr Bruna’s team believes that neuroblastoma cells use a flexible method called ‘phenotypic plasticity’ to adapt, survive treatment and lead to the cancer relapsing.
Evidence suggests that other cells present in tumours, immune cells that are supposed to fight cancer as part of our anti-tumour immune system, in some cases can be reprogrammed to help the neuroblastoma cells adapt to and survive treatment. In particular, Dr Bruna believes that immune system cells called macrophages could be key.
In this project, the researchers will use advanced techniques to study individual changes in cells behaviour within a mix of neuroblastoma and immune cell populations over time. This will help them identify the interplay between cell types (specifically, neuroblastoma cancer cells and macrophages) and understand the molecular and dynamic factors that control these networks. Dr Bruna’s team will explore whether macrophages influence or help neuroblastoma cells ability to adapt to treatment and regrow. They will also look at if and how neuroblastoma cells are able to corrupt macrophages to transform these into pro-tumour cells.
Dr Bruna wants to translate this knowledge into innovative treatment strategies. The goal is to test treatments that stop oncogenic interactions between neuroblastoma cells and macrophages and/or promote interactions that will favour anti-tumour immunity. Her team will look at substances that encourage macrophages to fight the tumour (i.e. factors that promote anti-tumour immunity), rather than support it. They also want to combine immune-based treatments with standard treatment to see if it makes the cancer worse at adapting and easier to kill.
The treatments will be tested in 3D tumours grown in the lab from patients’ neuroblastoma cells. This will ensure that any findings are relevant to patients. Dr Bruna hopes this project will lead to new treatment strategies for blocking treatment resistance, leading to better outcomes for young cancer patients.