Targeting short pieces of genetic code to treat malignant germ cell tumours

26 June 2014
Dr Matthew Murray, University of Cambridge

Malignant germ cell tumours are a varied group of tumours that occur mostly in the ovaries and testes but also at other sites including the brain. Dr Murray is focusing upon the development of a new treatment approach, targeting short pieces of genetic code known as microRNAs that are found at elevated levels in these tumours. Targeting microRNAs may be a ‘clean’, non-toxic therapy that could improve survival in young patients with germ cell tumours, with minimal risk of side effects.

Amount of grant: £149,252 | Date of award: June 2014

Overview

Malignant germ cell tumours (GCTs) are a varied group of tumours that affect children and young people. They occur mostly in the ovaries and testes but also at other body sites, including the brain.

At present, treatment may include a combination of chemotherapy, surgery and radiotherapy. Although most patients with malignant GCTs do well, some patients have poor outcomes, particularly those who relapse with tumours within the brain, and those whose tumours are resistant to conventional chemotherapy.

MicroRNAs are small pieces of genetic code that can suppress the production of proteins within our cells. Alterations of microRNA levels have been shown to cause the onset and progression of various cancers. Dr Murray and colleagues have identified two families of microRNAs that are at high levels in all malignant GCTs.

It has been shown that the effect of harmful levels of microRNAs can be blocked using molecules know as tiny LNAs (tiny ‘locked-nucleic-acid’ molecules). The team has designed tiny LNAs that will bind to the microRNAs, blocking their ability to suppress the protein production.

Malignant GCT cells will be treated with different amounts of the tiny LNAs to find the dose that blocks the action of these microRNAs best. The team will also look for unexpected effects of tiny LNAs on cells.

Because the two microRNA families that are abundant in malignant GCTs are present at very low levels in normal cells, the tiny LNAs should have very little effect on normal cells and there should therefore be a low risk of treatment-related side-effects.

About the research team

This is a very exciting new direction for oncology therapy and these investigators are at the forefront.
External reviewer
Dr Matthew Murray is an Academic Consultant Paediatric Oncologist whose laboratory work is internationally recognised. In collaboration with Professor Nicholas Coleman, co-investigator on this project, he has already published ground-breaking research on microRNAs in malignant GCTs.

The Coleman laboratory at the University of Cambridge has the necessary personnel, laboratory infrastructure to underpin this work and with their combined knowledge, expertise and understanding of the specialist field, Dr Murray and Professor Coleman are exceptionally well-placed to undertake this work.

What difference will this project make?

If, as expected, the treatment is successful in killing tumour cells with little effect on normal cells, this approach may be a ‘clean’, non-toxic therapy to improve survival of patients with high-risk malignant GCTs and reduce the effects of chemotherapy during treatment and in the following decades for patients with low-risk malignant GCTs. This is important, as treatment of patients with GCTs using current chemotherapy drugs is associated with significant toxicities such as hearing loss, kidney and lung impairment, heart disease and second cancers.

This exciting new technology also has the potential to be applied to other children’s cancers, in which altered levels of microRNAs have been identified.

Read more: Germ cell tumours | Side effects of treatment
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