Discovering more about the development of childhood germ cell tumours

The challenge

Germ cell tumours (GCTs) are cancers that come from the cells that develop into sperm or eggs (called primordial germ cells). Many children with these tumours can be cured, but treatments have serious long-term side effects and don’t work for all patients. Despite this, there have been no new treatment options in decades, largely because these tumours are so hard to study in the lab. 

GCTs include many different tumour types. Some closely resemble the original germ cells (germinomas and seminomas), others behave like early stem cells (embryonal carcinomas), some grow into mixed tissues such as brain, muscle or skin (teratomas), and others form structures similar to the placenta (yolk sac tumours and choriocarcinomas). In other words, GCTs can imitate almost any cell found in early human development. 

The project

In this project, Dr Harry Leitch’s team at UCL Great Ormond Street Institute of Child Health want to find out how one type of cell – the PGC – can turn into so many different types of tumours.

Thanks to recent advances, the researchers can study lab-grown PGCs for the first time. They have already had a key breakthrough with lab-grown PGCs – a recipe that can force them to revert back to a stem cell-like state, where the PGCs can produce a wider range of cell types. This mirrors a crucial step in how GCTs are thought to form in the body, a process the researchers call ‘in vitro germ cell tumorigenesis’ (ivGCT). 

During this process, PGCs produce stem cells – but they also produce unexpected cell types. The team plan to identify all of these cell types, work out how they develop, and test whether they match the range of cells found in real tumours.

The impact

Using the ivGCT system, the team will be able to test long-standing theories about how GCTs form for the first time. Any new understandings about how these tumours develop could point towards desperately needed new treatment strategies. 

Long term, Dr Leitch hopes that this project will form the foundations for the development of lab-grown tumours that truly resemble those found in children and young people. These could be used to safely test new therapies – something that cannot easily be done in patients.