Research points to kinder treatments for germ cell tumours

Germ cell tumours (GCTs) affect more than 2,300 children, teenagers, and young adults every year in the UK. These tumours arise from sperm- or egg-forming cells and thus occur in the testes and ovaries, but may also form also at other sites in the body, including the brain.

Although most patients diagnosed with GCTs have good outcomes, current treatment regimens that include conventional chemotherapy can lead to long-term effects that negatively impact the health and well-being of survivors.

Additionally, there are some patients, for example those with chemotherapy-resistant disease or who relapse after treatment, for whom cure rates are low. There is therefore a need for kinder, more effective treatments.

The research team at the Department of Pathology, University of Cambridge, have focussed on short pieces of genetic code termed ‘microRNAs’ (miRNAs). The team has previously shown that a small number of highly specific miRNAs are present at high levels in all malignant (cancerous) GCTs and are elevated in patient circulation at the time of malignant GCT diagnosis, allowing opportunities for more accurate diagnosis and monitoring.

In this work, now published in the British Journal of Cancer, the team tested a number of different methods of blocking the action of these miRNAs, and having successfully done so, found that this slowed down the growth of malignant GCT cells. They showed that this was in part due to the blockade of the effects of these miRNAs on cell division, in other words, on the cancer cells’ ability to divide rapidly.

First author Dr Shivani Bailey, said: “GCTs are an excellent ‘model’ for the concept of blocking the action of miRNAs, as in these tumours, just a small number of specific miRNAs are present at extremely high levels, and not present in normal body tissues. We anticipate that our work will benefit the cancer research field more widely, including in other childhood tumours.”

Senior author, Dr Cinzia Scarpini, Senior Research Associate at the Department of Pathology, University of Cambridge, added: “Work in our laboratory will now focus on further testing, including combining the blockade of these miRNAs with current chemotherapy drugs, with the ultimate aim of reducing the doses of drugs required to cure GCT patients, and with less side-effects”.

Dr Caroline Johnston, Senior Research Manager, Action Medical Research, who jointly funded the work, said: “Whilst we are some years from testing this work in a clinical setting, these results highlight how important the high levels of these short and specific pieces of genetic code, or miRNAs, are to germ cell tumour development and progression.

"These exciting developments demonstrate Action Medical Research’s commitment to funding pioneering research which could help more children with different types of cancer.”

Christiana Ogunbote, Head of Research at joint funder Children with Cancer UK, added: “We are delighted to have supported this groundbreaking work which targeted these miRNAs in this group of tumours, the treatment of which can often cause life-long impact on survivors. More work will be required to test these agents further, but we are very excited by the developments our fundraisers have helped support."

Reference
Bailey, S., Ferraresso, M., Alonso-Crisostomo, L. et al. Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption. Br J Cancer 129, 1451–1461 (2023). https://doi.org/10.1038/s41416-023-02453-1