New research from the Department of Pathology, University of Cambridge and CRUK Cambridge Centre Paediatric Cancer Programme members have identified a set of microRNAs in malignant germ cell tumours (GCTs), which may provide new treatment options for patients.
In this work, now published in the Molecular Oncology journal, the team identified a microRNA set at low levels in malignant GCTs. When these microRNAs were reintroduced into tumour cells and restored levels to normal, they inhibited cancer growth.
Furthermore, they identified other pathways in the cancer cells affected by this microRNA ‘replenishment’ strategy, which are also potentially targetable by currently available drugs. Further experimental work is warranted to study these cell line findings in more detail and more extensively.
Germ cell tumours (GCTs) arise from the cells responsible for producing eggs or sperm. During normal development, in early pregnancy, germ cells migrate to the ovaries and testes (‘gonads’) to form egg- or sperm-producing cells. However, the cells and/or the migration can go wrong, leading to the formation of GCTs either in the gonads or at ‘extragonadal’ sites such as the abdomen, chest, and brain.
In the UK, approximately 2,500 children, teenagers, and young adults are diagnosed with GCTs each year. Whilst most patients are cured, many face lifelong side effects. Additionally, some patients develop resistance to standard chemotherapy and may die of their disease. As a result, identifying kinder treatments that can improve overall cure rates whilst resulting in fewer long-term side effects is a priority.
The research team at the Department of Pathology, University of Cambridge, has extensive experience working with short pieces of genetic code, termed ‘microRNAs’, in malignant GCTs. They have already shown that a small number of highly specific microRNAs are found at high levels in malignant GCTs. They have shown that these microRNAs cause cancer growth, can be targeted experimentally to reduce growth, and are also found at high levels in a patient’s blood at the time of diagnosis. These findings allow opportunities for more accurate diagnosis and monitoring of the disease and potential future therapies.
Dr Marta Ferraresso
First author, Dr Marta Ferraresso, said, “These initial results are promising in identifying potential new targeted therapies. Further work is now required to study them in more detail. Employing more specific and less aggressive treatments will improve cure rates, reduce toxicity, and improve our patients’ quality of life. This important study will serve as a platform to work towards this goal for patients with malignant germ cell tumours.”
Dr Cinzia Scarpini
Senior author Dr Cinzia Scarpini, Senior Research Associate at the Department of Pathology, University of Cambridge, added, “Patients with germ cell tumours typically have a good prognosis, but there are considerable side-effects to current therapies. We must continue to work towards kinder yet more effective ways to treat these types of cancer. The published study is another step towards achieving this, and we are very grateful for the support we have received from funding bodies and families of affected children who have raised money to support us and made this work possible.”
Reference: Ferraresso et al. Replenishing co-downregulated miR-100-5p and miR-125b-5p in malignant germ cell tumours causes growth inhibition through cell cycle disruption [https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13757]