̽��ֱ�� of Cambridge - blood test

Blood test to monitor cancer up to ten times more sensitive than current methods

Anonymous — Wed, 17 Jun 2020 18:00:00 +0000

In the coming years, this method and others based on this approach could lead to tests that more accurately determine if a patient is likely to relapse after treatment and could pave the way for the development of pinprick home blood tests to monitor patients. ̽��ֱ��research, funded by Cancer Research UK, is published in the journal Science Translational Medicine

̽��ֱ��technique uses personalised genetic testing of a patient’s tumour to search blood samples for hundreds of different genetic mutations in circulating tumour DNA (ctDNA); DNA released by cancer cells into the bloodstream.

Combined with new methods to analyse this data to remove background noise and enhance the signal, the team was able to reach a level of sensitivity that in some cases could find one mutant DNA molecule among a million pieces of DNA – approximately ten times more sensitive than previous methods.

Dr Nitzan Rosenfeld, senior group leader at the Cancer Research UK Cambridge Institute who led the team that conducted this research, said: “Personalised tests that can detect if cancer is still present, or find it early if it is returning, are now being tested in clinical trials.

While this may be several years away from clinical use, our research shows what is possible when we push such approaches to an extreme. It demonstrates that the levels of sensitivity we’ve come to accept in recent years in relation to testing for ctDNA can be dramatically improved. At present this is still experimental, but technology is advancing rapidly, and in the near future tests with such sensitivity could make a real difference to patients.”

Detecting ctDNA in blood samples is what is known as a ‘liquid biopsy’. It allows doctors to find out more about a patient’s cancer without the need for invasive surgery. ̽��ֱ��technique is important for monitoring cancer patients, particularly after they’ve received treatment, as it can be an indicator of whether the treatment was successful and if the patient might relapse. In some situations, other types of tests can be used to detect some cancers before they display any symptoms or show up on a scan.

Currently, the sensitivity of the methods depends on having a high enough number of mutant pieces of DNA, either relative to background DNA or in absolute numbers. When the amount of ctDNA is low, a test can produce a negative result even if a patient has residual cancer in their body that could lead to relapse.

A single tumour will contain many different mutations that caused the cancer to form. While some of them are commonly known across certain cancer types, such as EGFR in lung cancer, the overall set of mutations for a tumour varies from person to person. By analysing the genetic makeup of an individual’s tumour and targeting a set of mutations in a personalised way, liquid biopsies to monitor cancer can become much more sensitive.

Until recently, these personalised liquid biopsies have searched for around 10-20 mutations in the blood and up to around 100 at most. In the material from a tube of blood, these would be able to detect ctDNA to levels on the range of one mutant molecule among 30,000 pieces of DNA.

This new technique looks for hundreds and sometimes thousands of mutations in each blood sample, routinely achieving a sensitivity of one mutant molecule per 100,000, and under optimal conditions can reach a level measured in parts per million.

̽��ֱ��researchers describe traditional liquid biopsies as like looking for a needle in a haystack. This new approach of using personalised genetic profiles to search for many different mutations rather than just one, increases the number of ‘needles’ that can be found, making chances of success more likely.

They also say the ‘haystack’ itself could be made smaller; as the methods developed for this research could mean that smaller and smaller amounts of blood could be required for the test to still work. Eventually, this could lead to tests that would require only a pinprick of blood – a procedure that patients could perform at home – that would then be sent to a lab for analysis. This would not only mean fewer visits to the hospital, but would also allow the patient to be more frequently monitored.

̽��ֱ��researchers and their collaborators studied samples from 105 cancer patients, testing the method on small sets of patients with five different cancer types, with both early and late stage disease.

̽��ֱ��method showed promising results and was able to detect ctDNA at high sensitivity in patients with advanced breast and melanoma cancer, and in patients with glioblastoma, which is notoriously difficult to detect in blood. ̽��ֱ��test was also able to detect ctDNA in patients with earlier-stage disease, where the level of ctDNA in the blood is much lower and difficult to find. This included patients with lung or breast cancer, as well as patients with early-stage melanoma who had already had surgery, which makes detection even more difficult.

In ongoing studies funded by Cancer Research UK, the team and their collaborators plan to use this method to measure ctDNA levels in individuals who are at high risk of developing cancer to help refine future tests for cancer early detection.

Michelle Mitchell, chief executive of Cancer Research UK, said: “Liquid biopsies have the potential to revolutionise all aspects of cancer care, from early detection to personalised treatment and monitoring. As a field that relies heavily on technology, this kind of proof-of-concept research is incredibly important for us to invest in as a charity, as it’s what makes potential future leaps in the use of liquid biopsies possible, and ultimately save more lives.”

Reference:
Jonathan C. M. Wan et al. ‘ctDNA monitoring using patient-specific sequencing and integration of variant reads.’ Science Translational Medicine (2020). DOI: 10.1126/scitranslmed.aaz8084

Adapted from a Cancer Research UK press release.

A new method of analysing cancer patients’ blood for evidence of the disease could be up to ten times more sensitive than previous methods according to new research led by the ̽��ֱ�� of Cambridge.

While this may be several years away from clinical use, our research shows what is possible when we push such approaches to an extreme

Nitzan Rosenfeld

NCI Center for Cancer Research

Human Colon Cancer Cells

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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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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Researchers discover new test for chronic blood cancers

sj387 — Tue, 10 Dec 2013 15:27:54 +0000

A simple blood test will soon be able to catch the vast majority of a group of chronic blood cancers, a new study reveals. Although around 60 per cent of cases can be identified with the current blood test, scientists did not know what caused the other cases and therefore could not test for it. Cambridge researchers have now identified a new cancer gene which accounts for the other 40 per cent of these chronic blood cancers. ̽��ֱ��research was published today, 10 December, in the New England Journal of Medicine.

Professor Tony Green, from the ̽��ֱ�� of Cambridge’s Cambridge Institute for Medical Research and Department of Haematology, who led the research said: “Diagnosing these chronic blood cancers is currently difficult and requires multiple tests, some of which are invasive and painful. Now, most patients with a suspected blood cancer will be able to be given a diagnosis after a simple blood test.”

This group of chronic blood cancers – which affect an estimated 30,000 people annually in the UK – cause the over-production of red blood cells and platelets. These changes result in an increased incidence of blood clots which can be devastating when strokes or heart attacks occur. Although many patients can live for years with few or no symptoms, in some patients the disorders can become more aggressive with time and may even develop into acute leukaemia.

In 2005 scientists identified the JAK2 gene, mutationt in which are associated with around 60 per cent of blood cell disorders. Based on these findings a blood test was developed which transformed the way these blood disorders are diagnosed. Unfortunately, because the gene was only found in a little over half of people with chronic blood cancers, individuals who tested negative for the JAK2 gene would then have to undergo a battery of protracted, invasive testing to determine if they indeed had one of these disorders.

In the new study, led by the ̽��ֱ�� of Cambridge and the Wellcome Trust Sanger Institute and supported by Leukaemia & Lymphoma Research together with the Kay Kendall Leukaemia Fund, scientists identified a new gene, CALR, which is altered in the other 40 per cent of blood disorders. For the research, the scientists sequenced the DNA of patients with chronic blood disorders. By analysing the DNA sequence, they were able to identify CALR as a new cancer gene which, when mutated, results in chronic blood cancers. Additionally, they found that patients with the CALR mutation – unlike those with the JAK2 mutation – had higher platelet counts and lower haemoglobin levels.

Peter Campbell from the Sanger Institute, who co-led the research, said: “There is now a sense of completeness with these disorders – the vast majority of our patients can now have a definitive genetic diagnosis made. In the next year or two, we will see these genetic technologies increasingly used in the diagnosis of all cancers, especially blood cancers.”

Dr Jyoti Nangalia co-first author of the study from the ̽��ֱ�� of Cambridge said: “Not only will the identification of CALR lead to a new, less invasive test, we also hope that it can lead to new treatments – just as the discovery of JAK2 did. ̽��ֱ��CALR gene is involved in a cell function – aiding with the folding of proteins made by the cell - which has not implicated in these disorders before, so our research raises as many questions as it answers.”

A new test for blood cancers will catch many more cases than the present test that identifies only 60 per cent.

Not only will the identification of CALR lead to a new, less invasive test, we also hope that it can lead to new treatments

Dr Jyoti Nangalia

Nephron

Micrograph of a plasmacytoma, a hematological malignancy

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