̽��ֱ�� of Cambridge - Nitzan Rosenfeld

Personalised blood test can detect persistent lung cancer

cjb250 — Thu, 17 Mar 2022 13:00:14 +0000

Scientists at the Cancer Research UK Cambridge Institute used a personalised blood test for patients, which is a type of liquid biopsy that can pick up tiny fragments of DNA that are released into the blood as tumours grow. This DNA, called circulating tumour DNA (ctDNA), can reveal the state of the tumour, its location and potentially its weaknesses, which could be used to select the best treatments.

̽��ֱ��results from the Lung Cancer Circulating Tumour DNA (LUCID-DNA) study, funded by Cancer Research UK, have been published today in the Annals of Oncology.

Many patients who are treated for early-stage non-small cell lung cancer can be cured with either surgery, radiotherapy or sometimes (chemo)radiotherapy.

After treatment, lung cancer patients are carefully followed up with tests including CT scans to find out if the treatment has removed the tumour, but scans won’t pick up tiny quantities of cancer cells known as minimal residual disease (MRD) which could still regrow into further tumours.

By finding signs that lung cancer cells might still be present and active after treatment, using methods such a liquid biopsy, doctors might be able make better choices about treating patients, aiming to improve the chances of survival for patients who are at higher risk while reducing side effects for patients who are at a lower risk group.

̽��ֱ��LUCID-DNA study aimed to find out if circulating DNA can be detected in early stage lung cancers. It used a liquid biopsy, called RaDaR™, which analyses up to 48 different mutations that are unique to each patient’s tumour. RaDaR™ was developed by Inivata, a biotech company co-founded by Dr Rosenfeld, and is based on technologies developed initially by his lab at the Cancer Research UK Cambridge Institute.

Dr Nitzan Rosenfeld, group leader at the Cancer Research UK Cambridge Institute, Chief Scientific Officer of Inivata and co-lead author of the study, said: “If cancer cells remain in the body after treatment a tumour can regrow. If that happens, it is a big setback for patients and the doctors treating them.

“Liquid biopsy can be used to detect tiny amounts of residual cancer after treatment, flagging those patients who have signs that their tumour may not have been eradicated completely with treatment. We’re hoping that this technology could help doctors decide when additional rounds of treatment are needed, and could save lives.”

To find out if liquid biopsy could find lung cancer patients with MRD, the LUCID-DNA study team enrolled 88 patients who were treated at Royal Papworth Hospital and Addenbrooke’s Hospital for early stage non-small cell lung cancer. This type of cancer accounts for over 85% of all lung cancer cases.

̽��ֱ��research team extracted DNA from tumour samples provided by the patients and sequenced the DNA to find combinations of mutations unique to each patient’s lung cancer. Using this genetic “fingerprint”, Inivata created a blood test which was personalised to the patient’s tumour.

̽��ֱ��liquid biopsies were then used to detect tumour DNA in blood samples collected before treatment, and for up to 9 months after treatment. ̽��ֱ��researchers found that patients who had tumour DNA present between two weeks and four months after treatment were much more likely to have their lung cancer come back or to die from it.

Professor Robert Rintoul, Professor of Thoracic Oncology at the ̽��ֱ�� of Cambridge, Honorary Respiratory Physician at Royal Papworth Hospital and co-lead author of the study, said: “We need to study these liquid biopsies further to find the best ways to deploy them, but these results clearly show that they can potentially be an effective tool to help decide which patients need further treatment.

“Being able to offer patients personalised monitoring and treatment will ultimately save more lives and help us to beat cancer sooner.”

Lung cancer is the third most common type of cancer in the UK. Every year, around 48,500 people are diagnosed with lung cancer and every year around 35,100 people die from the disease in the UK.

Aart Alders participated in the LUCID-DNA observational clinical study at Royal Papworth Hospital following his lung cancer surgery.

“I was first diagnosed with an early-stage lung cancer about five years ago and underwent a surgical operation to remove it,” he said. “Although some people need further treatment with chemotherapy, I have been very fortunate and my original lung cancer has not returned.

“I was very pleased to be able to help with the LUCID-DNA research study. By trying to develop a blood test to help doctors predict whether a lung cancer might come back or not, we will increase the chance of curing more people.”

Michelle Mitchell, Chief Executive of Cancer Research UK, said: “Lung cancer is one of the biggest killers in the UK. ̽��ֱ��earlier it is caught, the more likely it is to be treated successfully.

“Detecting signs of cancer before or after treatment without the need for invasive surgery has huge potential for both patients and doctors.

“I look forward to seeing more research that will develop liquid biopsy further, which will and ultimately make it much easier for doctors to offer treatment that best matches the patient’s needs, increasing their chance of survival.”

Adapted from a press release by Cancer Research UK

Patients who are at a higher risk of their lung cancer returning can be identified by a personalised blood test that is performed after treatment, according to researchers at the ̽��ֱ�� of Cambridge.

Liquid biopsy can be used to detect tiny amounts of residual cancer after treatment, flagging those patients who have signs that their tumour may not have been eradicated completely with treatment

Nitzan Rosenfeld

Belova59

Blood test

̽��ֱ��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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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

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̽��ֱ��Academy of Medical Sciences announces new Fellows for 2020

sc604 — Wed, 13 May 2020 01:00:00 +0000

̽��ֱ��new Fellows have been chosen for their exceptional contributions to advancing biomedical science via world-leading research discoveries, running national science communication and engagement programmes and translating scientific advances into benefits for patients and the public.

̽��ֱ��value of medical science has never been more apparent than during the current coronavirus global health crisis. From testing and vaccine development, to public health and behavioural science, to addressing the impacts of lockdown measures on mental health, biomedical and health scientists are helping to guide the UK through unprecedented challenges.

Several new Fellows have redirected their research efforts to tackle the effects of the pandemic, such as Professor Ludovic Vallier FMedSci, a stem cell expert from the ̽��ֱ�� of Cambridge, who has refocussed part of his team to study the effects of coronavirus on the liver. Professor Tamsin Ford CBE FMedSci, a Professor of Psychiatry at Cambridge, has channelled her expertise into looking at mental health impacts of the pandemic on children and young people.

Professor Sir Robert Lechler PMedSci, President of the Academy of Medical Sciences said: “This year our new Fellows announcement happens amidst a global health crisis. Never has there been a more important time to recognise and celebrate the people behind ground-breaking biomedical and health research, working harder than ever to further knowledge and protect patients and the public.

“It brings me great pleasure to congratulate the new Fellows, and see our Fellowship grow to even greater heights of evidence-based advice, leadership and expertise.”

̽��ֱ�� ̽��ֱ�� of Cambridge Fellows elected in 2020 are:

Professor Menna Clatworthy FLSW, NIHR Research Professor and Professor of Translational Immunology, ̽��ֱ�� of Cambridge and Associate Faculty, Wellcome Sanger Institute, Fellow, Pembroke College

Dr Helen Firth, Consultant Clinical Geneticist, Cambridge ̽��ֱ�� Hospitals, Honorary Faculty Member, Wellcome Sanger Institute, Bye-Fellow, Newnham College

Professor Tamsin Ford CBE, Professor of Child and Adolescent Psychiatry, ̽��ֱ�� of Cambridge, Fellow, Hughes Hall

Professor Ziad Mallat, Professor of Cardiovascular Medicine, ̽��ֱ�� of Cambridge

Dr Nitzan Rosenfeld, Senior Group Leader, Cancer Research UK Cambridge Institute, ̽��ֱ�� of Cambridge

Professor Ludovic Vallier, Professor of Regenerative Medicine, Wellcome - MRC Cambridge Stem Cell Institute, ̽��ֱ�� of Cambridge, Fellow, St Edmund’s College

̽��ֱ��new Fellows will be formally admitted to the Academy on 25 June 2020.

Six affiliates of the ̽��ֱ�� of Cambridge are among 50 world-leading UK researchers who have been elected to the prestigious Fellowship of the Academy of Medical Sciences.

Big T Images for Academy of Medical Sciences

Academy of Medical Sciences

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Scientists develop simple blood test to track tumour evolution in cancer patients

bjb42 — Thu, 02 May 2013 09:06:52 +0000

By tracking changes in patients’ blood, Cambridge scientists have created a new way of looking at how tumours evolve in real-time and develop drug resistance. ̽��ֱ��research was published in the print edition of Nature today, 02 May.

Scientists at the Cancer Research UK Cambridge Institute at the ̽��ֱ�� of Cambridge used traces of tumour DNA, known as circulating tumour DNA (ctDNA), found in cancer patients’ blood to follow the progress of the disease as it changed over time and developed resistance to chemotherapy treatments.

For the study, which was co-directed by Dr James Brenton, Professor Carlos Caldas, and Dr Nitzan Rosenfeld from the ̽��ֱ��'s Cancer Research UK Cambridge Institute, they followed six patients with advanced breast, ovarian and lung cancers and took blood samples, over one to two years. They then focused analysis on those samples that contained relatively higher concentrations of tumour ctDNA,

By looking for changes in the tumour ctDNA before and after each course of treatment, they were able to identify changes in the tumour’s DNA that were likely linked to drug resistance following each treatment session.

Using this new method they were able to identify several changes linked to drug-resistance in response to chemotherapy drugs such as paclitaxel (taxol) which is used to treat ovarian, breast and lung cancers, tamoxifen which is used to treat oestrogen-positive breast cancers and transtuzumab (Herceptin) which is used to treat HER2 positive breast cancers.

̽��ֱ��researchers hope this new approach could facilitate research on how cancer tumours develop resistance to some of our most effective chemotherapy drugs as well as providing an alternative to current methods of collecting tumour DNA – by taking a sample direct from the tumour – a much more difficult and invasive procedure.

Dr Rosenfeld said: “Tumours are constantly changing and evolving which helps them develop a resistance to many of the drugs we currently give patients to treat their disease. We’ve shown that a very simple blood test can be used to collect enough tumour DNA to suggest to us what parts of the cancer’s genetic code is changing and creating tumour resistance to chemotherapy or biologically-targeted therapies.

“We hope that our discoveries can pave the way to helping us understand how cancers develop drug resistance as well as identifying new potential targets for future cancer drugs.”

Dr Brenton added: "Importantly, this advance means that we will be able to screen a much larger number of genes in the blood to test if specific genetic changes in the cancer explain resistance to treatment. ̽��ֱ��low cost and high acceptability of a blood sample means that this can be done across hundreds or thousands of patients. This is vital to discover reliable clinical biomarkers."

Professor Caldas said: " ̽��ֱ��tracking of different cancer clones in real time using a liquid biopsy will have enormous value to identify drug resistance in the clinic and adjust therapy accordingly."

̽��ֱ��Cancer Research UK Cambridge Institute is a major research centre which aims to take the scientific strengths of Cambridge to practical application for the benefit of cancer patients. ̽��ֱ��Institute is a unique partnership between the ̽��ֱ�� of Cambridge and Cancer Research UK. It is housed in the Li Ka Shing Centre, a state-of-the-art research facility located on the Cambridge Biomedical Campus which was generously funded by Hutchison Whampoa Ltd, Cambridge ̽��ֱ��, Cancer Research UK, ̽��ֱ��Atlantic Philanthropies and a range of other donors. For more information visit www.cruk.cam.ac.uk.

Story adapted from CRUK press release.

For more information about this story, please contact: Genevieve Maul, Office of Communications, ̽��ֱ�� of Cambridge. Email: Genevieve.Maul@admin.cam.ac.uk; Tel: 01223 765542.

Research sheds light on how tumours develop drug resistance

We hope that our discoveries can pave the way to helping us understand how cancers develop drug resistance

Nitzan Rosenfeld

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Blood test reveals women's response to breast cancer treatment

gm349 — Wed, 13 Mar 2013 14:22:30 +0000

Researchers at the Cancer Research UK Cambridge Institute at the ̽��ֱ�� of Cambridge took regular blood samples from 30 women with advanced breast cancer that had spread.

They used three biomarkers – circulating tumour DNA, levels of a protein called Cancer Antigen 15-3 (CA 15-3) and free-floating tumour cells – which can measure how advanced the disease is.

̽��ֱ��researchers compared these results with CT scans to see if changes in the biomarkers matched up with changes in the cancer.

They found that, out of the three biomarkers, tumour DNA in women’s blood gave the most accurate ‘real time’ picture of changes taking place in the body.

Professor Carlos Caldas, senior group leader at the Cancer Research UK Cambridge Institute and co-lead author of the study, said: “This study offers a practical application of cancer genomics and highlights the potential of personalised cancer medicine. By understanding the point at which a cancer changes we can select the most effective treatments and minimise side effects for patients.

“We can use blood samples to track how breast cancer is progressing as fragments of DNA are shed by cancer cells when they die, meaning they can be detected in blood samples using sensitive new sequencing techniques. ̽��ֱ��levels of tumour DNA are telling us how the cancer is responding to treatment.”

̽��ֱ��research was part-funded by Cancer Research UK and supported by the Experimental Cancer Medicine Centre and National Institute for Health Research Biomedical Research Centre at the Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust.

Dr Nitzan Rosenfeld, group leader at the Cancer Research UK Cambridge Institute and co-lead author of the study, said: “This work marks an important step in establishing circulating tumour DNA as a key biomarker for monitoring advanced breast cancer patients.

“By rigorous comparison to markers such as circulating tumour cells and CT imaging, we have shown that personalised genomic tests provide a sensitive and non-invasive measure of cancer spread and response to treatment. We also showed that these can be measured effectively by a variety of practical methods.”

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “These results hold the promise of a system that could allow us to modify someone’s treatment as their cancer changes, and they suggest an exciting way to quickly get hold of the personal details of a cancer, to target it for the most effective therapy.

“One of the things that will help our scientists design better cancer treatments is a way of measuring early on which ones are working and which are not. If we can find the molecular footprints of cancers during treatment and see how they change, we hope we will be able to track them down and remove them much more efficiently.”

Story provided by the CRUK.

For more information about this story, please contact: Genevieve Maul, Office of Communications, ̽��ֱ�� of Cambridge. Email: Genevieve.Maul@admin.cam.ac.uk; Tel: 01223 765542.

Breast tumour DNA circulating in the bloodstream could be used to measure how well a woman’s cancer is responding to treatment, according to a new study published in the New England Journal of Medicine.

̽��ֱ��levels of tumour DNA are telling us how the cancer is responding to treatment

Carlos Caldas

̽��ֱ�� of Cambridge: Johnny Settle

DNA

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