Low cost, safe and accurate test could help diagnose rare childhood cancers

cjb250 — Wed, 16 Dec 2015 00:00:11 +0000

Reported today in the British Journal of Cancer, the test could enable doctors to monitor the effectiveness of treatments without exposing patients to repeated doses of radiation.

̽��ֱ��target of the test is a type of cancer known as germ cell cancer. Germ cells are those cells in the body that go on to develop into sperm and egg cells. Germ cells can develop into tumours – both benign and malignant – particularly in the testes or ovaries, where the cells are normally found. However, occasionally germ cells can get trapped in the wrong part of the body during development and may later turn into brain tumours, for example.

̽��ֱ��five year disease-free and overall survival rates for patients with high-risk malignant germ cell tumours remains less than 50%, and so accurate diagnosis and monitoring is crucial to improving outcomes for patients. All of the current tests are expensive, and none are ideal.

̽��ֱ��most reliable diagnostic method currently in use is biopsy, where a section of the suspected tumour is extracted surgically and analysed by a pathologist. However, biopsies are prone to sampling errors and so may not be representative of the tumour as a whole. Computerised tomography (CT) scans and magnetic resonance imaging (MRI) also provide useful information but are not diagnostic and do not discriminate between benign and malignant tumours.

̽��ֱ��ideal tool for diagnosis would be a non-invasive blood test; however, currently available tests only identify around three in five malignant germ cell tumours, potentially delaying diagnosis and the ability to prioritise patients for surgery. Accurate disease monitoring with routine blood testing is not possible for two in five patients, requiring follow up CT scans with exposure to harmful radiation and an associated increased secondary cancer risk.

“Although relatively rare, childhood germ cell tumours need to be diagnosed accurately and followed up carefully to give us the best chances of treating them,” says Professor Nick Coleman from the Department of Pathology, ̽��ֱ�� of Cambridge. “At the moment, we are not good enough at diagnosing these tumours and monitoring their treatment: we need better, safer and more cost-effective tests.”

In research funded by Sparks charity, Great Ormond Street Hospital Children’s Charity and Cancer Research UK, researchers at the ̽��ֱ�� of Cambridge have developed a test for blood and cerebrospinal fluid samples that looks for a specific panel of four pieces of short genetic code known as microRNAs, which are found in greater quantities in malignant germ cell tumours. ̽��ֱ��test can distinguish malignant germ cell tumours from benign germ cell tumours and other cancers. ̽��ֱ��test can be used for diagnosis of malignant germ cell tumours in any part of the body, including the brain.

̽��ֱ��test can also be used to check the effectiveness of treatments and, as it is safe and cost-effective, allows for frequent testing to monitor for the recurrence of malignant germ cell tumours.

Dr Matthew Murray from the Department of Paediatric Haematology and Oncology, Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, says: “This test, developed with Dr Emma Bell, a postdoctoral scientist in our laboratory, could be exactly what we need: it could help us diagnose malignant germ cell tumours cheaply, safely and above all, more accurately than current methods. Our next step is to confirm our findings in a large clinical trial and, if this is successful, we hope to see the test in routine use in hospitals in the near future.”

Reference
Murray, MJ, Bell E, et al. A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours. British Journal of Cancer; 15 Dec 2015

A non-invasive, low cost blood test that could help doctors diagnose some types of malignant childhood tumour has been developed by researchers at the ̽��ֱ�� of Cambridge and Addenbrooke’s Hospital, Cambridge ̽��ֱ�� Health NHS Foundation Trust.

At the moment, we are not good enough at diagnosing these tumours and monitoring their treatment: we need better, safer and more cost-effective tests

Nick Coleman

̽��ֱ�� of Cambridge

Addenbrooke's Hospital

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Scientists discover a molecular ‘switch’ in cancers of the testis and ovary

gm349 — Thu, 01 Aug 2013 06:19:00 +0000

Cambridge scientists have identified an ‘on/off’ switch in a type of cancer which typically occurs in the testes and ovaries called ‘malignant germ cell tumours’. ̽��ֱ��research was published today, 01 August, in the journal Cancer Research.

Malignant germ cell tumours arise in sperm- or egg-forming cells and usually occur in the reproductive organs, the testes or ovaries. ̽��ֱ��cancerous tumours are seen in patients of all ages, both in childhood and adulthood.

Although many patients do well after treatment, current chemotherapy treatments can have severe long-term side effects, including hearing loss and damage to the kidneys, lungs and bone marrow. For some patients, outcomes remain poor and testicular cancer continues to be a leading cause of death in young men.

̽��ֱ��scientists found that all malignant germ cell tumours contain large amounts of a protein called LIN28. This results in too little of a family of tiny regulator molecules called let-7. In turn, low levels of let-7 cause too much of numerous cancer-promoting proteins in cells. Importantly, the cancer-promoting proteins include LIN28 itself, so there is a vicious cycle that acts as an ‘on’ switch to promote malignancy. ̽��ֱ��researchers have likened these changes to a ‘cascade effect’, extending down from the large amounts of LIN28 to affect many properties of the cancer cells.

̽��ֱ��researchers also discovered that by reducing amounts of the protein LIN28, or by directly increasing amounts of let-7, it is possible to reverse the vicious cycle. Both ways reduced levels of the cancer-promoting proteins and inhibited cell growth. Because the level of LIN28 itself goes down, the effects are reinforced and act as an ‘off’ switch to reduce cancerous behaviour.

Nick Coleman, Professor of Molecular Pathology, Cambridge ̽��ֱ�� said: “We need new ways of treating patients with malignant germ cell tumours to minimise the toxic effects of chemotherapy and to improve survival rates when tumours are resistant to treatment. Having identified this ‘on/off’ switch, it will now be important to identify new drugs that can be used to keep it in the ‘off’ position.”

Dr Matthew Murray, Academic Consultant in Paediatric Oncology, Addenbrooke’s Hospital, Cambridge said: “ ̽��ֱ��switch effect that we have discovered is present in all malignant germ cell tumours, whether they occur in males or females, young or old. Such a fundamental abnormality makes an excellent new target for treating these tumours.”

Susanne Owers, Director of Fundraising at Addenbrooke’s Charitable Trust, which funded this research, said: “We are delighted to have supported this study, which has identified a key protein that triggers this type of cancer. ACT funds clinical academic researchers, like Dr Murray and Prof Coleman, because they are perfectly positioned to understand the clinical problems, working closely with patients, an insight not available to all researchers. Studies like this have the potential to make a tangible difference to patients, by identifying targets for the development of new drugs which may improve survival and have less side-effects compared with standard chemotherapy treatments. By funding this research, ACT – with the help of our supporters – can make a powerful contribution, enabling ground breaking research to be performed.”

Research could lead to new drugs to turn ‘switch’ off.

We need new ways of treating patients with malignant germ cell tumours to minimise the toxic effects of chemotherapy and to improve survival rates when tumours are resistant to treatment.

Professor Nick Coleman

Nick Coleman

Cancerous cells

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̽��ֱ�� of Cambridge - Nick Coleman

Low cost, safe and accurate test could help diagnose rare childhood cancers

Scientists discover a molecular ‘switch’ in cancers of the testis and ovary