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Detecting pancreatic cancer through blood tests

Pancreatic ductal adenocarcinoma (PDAC) makes up 95% of all pancreatic cancer cases and has the lowest survival rate, and early diagnostic methods have yet to be developed. As a result, diagnosis often comes at a later stage when treatment options are limited and prognosis is poor.

Diagnosis at this stage often comes from imaging techniques followed by tissue biopsies, which are not appropriate options to use as standardised, early screening methods. New ways to diagnose PDAC at an earlier stage are needed, without the use of invasive procedures.

Liquid biopsies are becoming a more popular option to fill this demand. Taking a blood sample is minimally invasive, quick, and can tell us a lot of information about a person from their cfDNA (cell free DNA). cfDNA is released from cells and circulates in the blood, containing information about the cell they come from.

Methylation on cfDNA often appears in cancer patients, making it an effective biomarker that can be used to diagnose the presence of cancer with high accuracy and specificity about the cancer (such as location). The concept has many applications, including in the earlier diagnosis of PDAC.

The identification of these biomarkers in blood is often limited to the technology used, with DNA being damaged by the harsh chemicals that are used in the processing. The recent development of TAPS technology at the University of Oxford has helped to overcome this, using a bisulphate-free method, and making it a perfect method for PDAC biomarker identification.

DPhil students Paulina Siejka-Zielinska and Felix Jackson and Postdoctoral Researcher Jingfei Chang from Dr Chunxiao Song’s lab in collaboration with Dr Shivan Sivakumar (consultant medical oncologist) have been investigating TAPS as a method to identify PDAC biomarkers. Using blood samples from PDAC patients and healthy individuals, they are applying TAPS technology to prove that it can be used to accurately detect pancreatic cancer biomarkers in cfDNA.

Preliminary results from this study suggest that cfDNA methylation can be used for the identification of PDAC, as well as being able to accurately distinguish between pancreatic cancer and other pancreatic disorders that effect the DNA, such as pancreatitis.

If this is the case, then the results from this study will make for solid grounds for the application of TAPS in the earlier screening for pancreatic cancer.

About the Song Lab

The Song Lab combine various chemical biology and genome technologies to develop novel tools to analyse the epigenome. The lab apply these tools to two main research areas: the use of epigenetic modifications in circulating cell-free DNA from the blood for non-invasive disease diagnostics including early detection of cancer, and understanding the contribution of epigenetic heterogeneity in cancer development.

Most recently, the TAPS technology developed at the Song Lab has led to the creation of the start up Base Genomics, which has been launched to set a new gold standard in DNA methylation detection using this TAPS technology. Base Genomics will initially focus on developing a blood test for early-stage cancer and minimal residual disease. You can read more about it here.

$410 million buy out for Oxford cancer detection technology

Biotechnology company, Base Genomics, launched in June 2020 based on Oxford’s Dr Chunxiao Song’s innovative TET-assisted pyridine borane sequencing (TAPS) technology. This week, Base Genomics was bought out by Exact Sciences for $410 million.

TAPS is a new method for measuring DNA methylation, a chemical modification on cytosine bases. DNA methylation is frequently altered in cancer and these altered DNA methylation levels are preserved in the small amounts of DNA that are released into the blood from cancer cells. With its enhanced sensitivity over the standard methodology for measuring DNA methylation, TAPS has great potential as the basis for a multi-cancer blood test.

“This acquisition by Exact Sciences will enable us to accelerate the clinical and commercial development of Base Genomics and unlock a new era for early cancer detection. This is a big step forwards”

says Base Genomics co-founder and chemistry lead, Dr Yibin Liu, who co-invented the technology while a post-doc at the Ludwig Institute for Cancer Research, Oxford Branch.

Exact Sciences will continue to build on the Base Genomics team in Oxford, creating a world-leading research centre for early stage cancer detection.

“I am thrilled that the TAPS technology developed in my lab has received this level of investment. We can now proceed much more rapidly to fully leverage the power of this technology for cancer detection and patient benefit”

says Dr Chunxiao Song, Assistant Member of the Ludwig Institute for Cancer Research, Oxford Branch and Base Genomics co-founder.

Chunxiao Song’s research has received funding from the Ludwig Institute for Cancer Research, Cancer Research UK and the NIHR Oxford Biomedical Research Centre. TAPS is continuing to be developed in Chunxiao’s lab, for example it was recently adapted for long-read sequencing, to further its application to other fields of biomedical research.

Understanding breast cancer risk in Chinese populations

Obesity has long been associated with an increased risk of breast cancer in post-menopausal women. But the relationship between obesity and breast cancer is less clear in pre-menopausal women. Moreover, a lot of uncertainty remains around the associations between body weight and breast cancer in countries such as China, where the average BMI is lower than in western countries, along with differences in the prevalence of other risk factors between western and eastern cultures. There is a need to better understand how morphological and lifestyle differences between populations may influence cancer incidence, in order to better understand and identify who is at an increased risk.

An upcoming study from the Clinical Trial Service & Epidemiological Studies Unit (CTSU) at the Nuffield Department of Population Health, led by Dr Christiana Kartsonaki and Dr Ling Yang, is investigating breast cancer incidence in Chinese populations in relation to adiposity measures such as BMI, waist circumference and body fat percentage.

The team used data from the China Kadoorie Biobank, a cohort study that has collected information from over half a million individuals from China since 2004. During an average of 10 years of follow-up of this cohort, there were 2,053 cases of breast cancer, which allows the team to assess what demographic or lifestyle factors might be influencing risk in Chinese women.

Early results suggest that, like western populations, increased levels of adipose tissue leading to higher BMIs are associated with higher risks of breast cancer in Chinese women, particularly among post-menopausal women. These results highlight the importance of understanding relative cancer risk factors between different ethnicities. Whilst some factors such as obesity are often common causes of cancer across all populations, there are many key biological and lifestyle factors that differ between western and eastern populations. Understanding how these may impact cancer risk in different ways will allow researchers to inform policy, so that clinicians may better identify who may have a higher risk of developing cancer.

About the CTSU

The Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) aims to generate and disseminate reliable evidence from observational epidemiology and from randomised trials that leads to practicable methods of avoiding premature death and disability.

This project is being led by Dr Christiana Kartsonaki and Dr Ling Yang in conjunction with Prof. Zhengming Chen.

Using big data in breast cancer research

Breast cancer is the most common type of cancer found in the UK population, with 1 in 8 women diagnosed during their lifetime. As a prevalent cancer, it’s important to understand more about the potential causes and relative risks that individuals from different demographics might have.

The Cancer Epidemiology Unit (CEU) at the Nuffield Department of Population Health specialises in large-scale studies into the lifestyle and genetic risk factors of cancers such as breast cancer. In doing so, these studies can provide evidence to inform public health policies and answer outstanding questions about how cancers may arise.

The cause of breast cancer has long been researched and over the last two decades, findings from the Unit’s large prospective studies and international collaborations have helped clarify the role of many risk factors for the disease, including use of menopausal hormones and oral contraceptives, as well as factors relating to childbearing. Within the last year, an updated review of the worldwide evidence carried out in CEU showed that menopausal hormone usage increases the long term risk of breast cancer by almost twice as much as was previously thought, findings which influenced public health guidance. Other recent work found evidence to suggest that high fruit and fibre intake and physical activity may be associated with lower risks of breast cancer.

The CEU work with big data, such as its Million Women Study which contains data from 1.3 million UK women, collected since it began  in 1996. The study includes 1 in 4 of all UK women born between 1935 and 1950 and remains the largest data set of its kind. The study, which aims to resurvey women every 3-5 years, continues to collect information on new potential risk factors such as working night-shifts (which in this case was shown to have no influence on breast cancer incidence).

Enhancing the quality and quantity of the Million Women Study dataset is high on the CEU’s agenda. One area of research where the study hopes to be able to contribute substantially over the next few years is in risk stratification for breast cancer. Prediction models which can be used to assess an individual’s breast cancer risk are key for planning risk-based screening approaches that are tailored to an individual, so refining their accuracy is important to ensure that interventions can be targeted appropriately. However, while existing risk prediction models look promising they need further improvement in their ability to identify those women who are most likely to get breast cancer before they can be applied at a population level. In particular, models should ideally incorporate the whole spectrum of breast cancer risk factors including genetic variation and radiological imaging data.

This will be the next stage for the Million Women Study, as Prof Gill Reeves, Head of the CEU, hopes to integrate new datasets into the study. This includes digital screening images from mammograms, and other clinical information, which could be used in combination with existing information held on participants, to allow the CEU to develop more accurate risk prediction models from the Million Women’s Study.

Prof Gill Reeves, Head of the CEU, says:

“Enriching the quality of datasets such as the Million Women Study will allow us to continue to provide reliable evidence regarding the effects of behavioural and biological factors on breast cancer risk, and help identify women who are at particularly high risk of the disease. In doing so, we can better inform public health advice, and clinical practice.”

To read more about the CEU’s work on breast cancer go to the  CEU website.

About the CEU

The CEU runs the Million Women’s Study (MWS) and EPIC-Oxford (two large cohort studies). Recent grant funding from CRUK has allowed for further enhancement of the MWS so that new clinical data and other potential risk factors for cancer may be integrated.

Prof Gill Reeves, Head of the CEU, is a Professor of Statistical Epidemiology. Her main research interests are the roles of hormonal and other risk factors in the development of female cancers.  She is particularly interested in risk factors and patterns of survival for molecular subtypes of breast cancer.

 

Funding boost for OxPLoreD early detection study

OxPLoreD is an observational cohort study sponsored by Johnson and Johnson that will recruit 1650 patients from across the UK with pre-cancerous lymphoproliferative disorders. These conditions include monoclonal B-cell lymphocytosis and monoclonal gammopathy of unknown significance that put individuals at higher risk of developing the blood cancers chronic lymphocytic leukaemia and multiple myeloma respectively.

The aim of the study is to look for new ways to find and treat blood cancer sooner by identifying clinical, genomic and immunological predictive markers of progression from these pre-cancerous conditions to malignant disease. The study will also explore the possibility of a future early intervention trial for the subgroup of patients at highest risk of progression.

OxPLoreD is one of the seven clinical trials that have received an £8m funding boost from UK Research and Innovation (UKRI) and will work in partnership with Genomics England. The funding will speed up the adoption of whole genome sequencing in the study of cancer. Genetic analysis is a critical tool that can allow clinicians to select the most appropriate treatments for each patient. In the OxPLoreD study, genetic analysis might be able to identify individuals at highest risk of disease progression that would benefit from earlier treatment. In the longer term this may also enable the identification of those people who would benefit from certain types of treatment.

Alison Cave, UKRI challenge director says:

“Research tells us that one-in-two people in the UK population will get cancer. That stark statistic shows just how important it is for us to seek new treatments. The use of genetic analysis opens new possibilities in our drive to beat cancer. The projects for which we have announced funding today are exciting pointers to future diagnosis and precision treatments”

The funding has been delivered through UKRI’s Industrial Strategy Challenge Fund’s £210m data to early diagnosis and precision medicine (DEDPM) programme. The challenge aims to combine research data and evidence from the NHS to create new and improved ways of identifying disease and treatment pathways.

Prof. Sir Mark Caulfield, Chief Scientist at Genomics England says:

“The 100,000 Genomes Project, Genomics England has analysed the genomes of over 17,000 cancer participants and this suggests that up to half have revealed mutations of potential clinical significance. The DEDPM programme is a major opportunity to expand the application of whole genome sequencing into clinical trials involving cancer where support from the ISCF is likely to deliver significant clinical benefit”

For more information about the other trials funded by this scheme, see the UK Research and Innovation announcement.

Oxfordshire-based SCAN pathway wins BMJ award

Every year, the British Medical Journal (BMJ) runs a competition to find the cancer care team that has developed new approaches to improve cancer diagnosis and treatment. This year, six teams were shortlisted from across the UK and on the 7th October it was announced that the Oxfordshire-based SCAN pathway had won this year’s award.

The Suspected CANcer (SCAN) pathway is designed to accelerate cancer diagnosis in patients with non-specific cancer symptoms. The UK performs worse than many other developed nations in terms of cancer survival and this is in part due to the fact that 21% of cancers are diagnosed after emergency presentation, when they are often at a later stage and more difficult to treat successfully.

In an effort to improve these statistics, urgent referral pathways for suspected cancer have been developed for symptoms specific to one cancer site. However, one in five people diagnosed with cancer only ever report non-specific symptoms of cancer, such as unexplained weight loss, fatigue, nausea, or abdominal pain. These people often experience delays due to being referred sequentially to multiple different tumour site-specific clinics before receiving a diagnosis. The SCAN team identified this unmet need and designed and implemented a new diagnostic pathway that straddles primary and secondary care for patients with non-specific but concerning cancer symptoms.

Patients are referred by their GP to the pathway based in the Churchill Hospital, Oxford, where they are investigated with a whole body computed tomography (CT) scan and undergo blood and stool testing. The outcome of these tests directs the patient to the most appropriate clinical expertise to reach a diagnosis as quickly as possible.

Since its implementation across Oxfordshire in November 2017, the SCAN pathway has seen 2148 patients and diagnosed 201 incidences of cancer, most commonly lung, bowel, pancreas, lymphoma and breast. In addition to cancer diagnoses, the SCAN pathway has diagnosed a large number of serious non-cancer conditions, including tuberculosis, endocrine diseases and inflammatory bowel disease.

“One of the unique features of the SCAN Pathway is that for the remaining patients who do not receive a cancer diagnosis, we offer GPs the option for these patients to have a general medical review in a further attempt to reduce onward referrals.”

  • Julie-Ann Moreland, Macmillan Project Manager and SCAN Navigator, Oxford Radiology Research Unit

Since the SCAN pathway’s inception, the number of GP surgery visits and secondary care referrals prior to receiving a cancer diagnosis decreased by approximately 4-fold, saving a large number of NHS appointments, and the time to diagnosis has reduced. Patients have also responded positively about the service in patient satisfaction questionnaires.

“Prior to the SCAN pathway, patients with non-specific symptoms were having to go to the GP on average 7.8 times and be referred to numerous secondary care clinics before receiving a diagnosis. The SCAN pathway decreases the time to diagnosis and allows patients to start receiving important treatments earlier. This will not only improve patient outcomes but will also reduce the anxiety experienced by patients while waiting for a diagnosis”

 

 “I am delighted that the SCAN team have received this recognition from the BMJ. The judges made a special mention of the holistic care that the clinical team works so hard to provide. Given its success, we are introducing the pathway across the Thames Valley Cancer Alliance and other regions. We are gathering data as we go so we can learn how to improve the service for patients.”

  • Dr Brian Nicholson, Academic GP Lead, Nuffield Department of Primary Care Health Sciences

 

“The development and implementation of the SCAN Pathway has been the result of hard work and collaborative teamwork with passionate people who have strived to develop a service focusing on improving the experience for patients.

“To even be short listed for this award is an incredible achievement and so to win it has been a fantastic and unexpected surprise. We are all very proud of this new pathway and this is a brilliant way to receive recognition and celebrate that.”

  • Zoe Kaveney, Cancer Programme Manager at Oxfordshire Clinical Commissioning Group

 

The SCAN pathway was supported by the Accelerate, Coordinate, Evaluate (ACE) programme funded by NHS England, Cancer Research UK and Macmillan, and the Oxfordshire Clinical Commissioning Group.

Using machine-learning approaches to identify blood cancer types

Myeloproliferative Neoplasms (MPNs) are a group of blood cancers that occur when stem cells in the bone marrow develop mutations that lead to over-production of blood cells – either red blood cells in Polycythaemia Vera (PV), or platelets in Essential Thrombocythaemia (ET). This carries an increased risk of developing blood clots, such as in the legs, lungs, heart attacks or strokes.

In myelofibrosis, the most severe of the MPNs, destructive scarring (‘fibrosis’) of the bone marrow develops, leading to failure of the marrow to produce blood cells and severe symptoms. Patients with all MPNs are at higher risk of developing leukaemia, especially patients with myelofibrosis when this develops in over 1 in every 10 patients.

Unfortunately, we do not yet have any drug treatments that can cure these conditions. Treatments for ET and PV aim to control the blood counts and reduce the risk of blood clots. For myelofibrosis, targeted therapies such as ruxolitinib, a JAK inhibitor, can effectively control symptoms, but this does not alter the natural history of the disease and survival remains less than 5-10 years following diagnosis.

In the vast majority of cases, mutations are found in one of 3 genes – JAK2, CALR or MPL. Screening for these is important in MPN diagnosis, however distinguishing between the MPN subtypes requires a careful examination of blood counts and the morphological features of a bone marrow biopsy.

Unfortunately, assessment of the bone marrow is highly subjective, reliant on qualitative observations and there is great variability, even when it is done by expert haematopathologists. In particular, it is very hard to reliably distinguish between a mutation-negative MPN and a ‘reactive’ (non-cancer) bone marrow.

A more accurate method for diagnosis is very much needed, to enable selection of the most appropriate treatment strategy for patients and to determine treatment targets. Megakaryocyte cells or  ‘megas’ – the large, bone marrow cells that produce blood platelets – are very abnormal in all the MPNs and thought to play a key role in the disease pathology. Interestingly, although the gene mutations underlying all 3 MPNs lead to an over production of megas, subtle differences in the appearance and location of these cells within the bone marrow occur in the different MPN subtypes.

To try to improve MPN classification, a team lead by Jens Rittscher (Department of Engineering) and Daniel Royston (Radcliffe Department of Medicine), developed an AI approach to screen and classify MPN cases based on features of the mega cells, discovering new features in their cell size, clustering and internal complexity. Their machine learning approach revealed that there are clear differences between MPN subtypes – the platform was able to more accurately classify patients by assessing subtle morphological differences in the biopsies that could not have been identified by the naked eye.

These findings have been published in Blood Advances. Dr Beth Psaila, a clinician scientist at the MRC Weatherall Institute of Molecular Medicine and a haematology consultant specialising in MPNs said:

“It has long been recognised that a multitude of subtle differences in megakaryocyte morphology can distinguish between the MPN subtypes. However, this means that assessment of bone marrow biopsies is poorly reproducible, sometimes leading to diagnostic uncertainty and inappropriate treatment plans for patients.

“The approach developed here is really exciting for the field, as it is now possible to perform deep phenotyping of megakaryocytes and more accurate disease classification using simple H&E slides which are routinely prepared in all diagnostic facilities. This will be incredibly useful both for research aimed at better understanding the role of megakaryocytes in blood cancers as well as improving diagnosis and treatment pathways for our patients.”

The team hopes that in the future, this work can be combined with other histological assessments to optimise the clinical application of AI approaches, and create a more comprehensive quantitative description of the bone-marrow microenvironment and its cancers.

About the researchers and the study

This work was funded by the NIHR Oxford Biomedical Research Centre and is the result of collaboration between Korsuk Sirinukunwattana (Department of Engineering), Alan Aberdeen (Ground Truth Labs Ltd.), Helen Theissen (Department of Engineering), Jens Rittscher (Department of Engineering) and Daniel Royston (Radcliffe Department of Medicine [NDCLS]).

Jens Rittscher is a Principle Investigator whose research aim is to enhance our understanding of complex biological processes through the analysis of image data that has been acquired at the microscopic scale. Jens develops algorithms and methods that enable the quantification of a broad range of phenotypical alterations, the precise localisation of signalling events, and the ability to correlate such events in the context of the biological specimen.

Korsuk Sirinukunwattana is a postdoctoral research assistant in Rittscher’s group specialised in medical image analysis and computational pathology. His main research interest is the association between tissue morphology and molecular/genetic subtypes in various diseases.

Alan Aberdeen leads Oxford spinout Ground Truth Labs, a company supporting digital pathology research through on-demand analysis, biomarker discovery, and high-quality cohorts.

Helen Theissen is a doctoral research student in Rittscher’s group. Her research focuses on computational methods to characterise cellular subtypes and quantify the bone marrow microenvironment in MPNs.

Daniel Royston is a joint academic & consultant Haematopathologist at Oxford University Hospitals NHS Foundation Trust / Radcliffe Department of Medicine.

Oxford to lead new programme of AI research to improve lung cancer screening

UK Research and Innovation, Cancer Research UK and industry are investing more than £11 million in an Oxford-led artificial intelligence (AI) research programme to improve the diagnosis of lung cancer and other thoracic diseases.

Professor Fergus Gleeson at the University of Oxford will lead on a programme of research focusing on accelerating pathways for the earlier diagnosis of lung cancer. Lung cancer is the biggest cause of cancer death in the UK and worldwide, with £307 million/year cost to the NHS in England. The earlier that lung cancer is diagnosed, the more likely that treatment will be successful but currently only 16% patients are diagnosed with the earliest stage of the disease. To address this clinical problem, NHS England is launching a £70 million lung cancer screening pilot programme at 10 sites*.

To improve patient care beyond the current screening guidelines, a team of academics from Oxford University, Nottingham University, and Imperial College London; NHS clinicians from Oxford University Hospitals NHS Trust, Nottingham University Hospitals NHS Trust, the Royal Marsden Hospital, the Royal Brompton Hospital, and University College London Hospitals NHS Foundation Trust; and the Roy Castle Lung Cancer Foundation will join forces with three leading industrial partners (Roche Diagnostics, GE Healthcare, Optellum).

Working with the NHS England Lung Health Check programme, clinical, imaging and molecular data will be combined for the first time using AI algorithms with the aim of more accurately and quickly diagnosing and characterising lung cancer with fewer invasive clinical procedures. Algorithms will also be developed to better evaluate risks from comorbidities such as chronic obstructive pulmonary disease (COPD). In addition, this programme will link to data from primary care to better assess risk in the general population to refine the right at-risk individuals to be selected for screening. It is hoped that this research will define a new set of standards for lung cancer screening to increase the number of lung cancers diagnosed at an earlier stage, when treatment is more likely to be successful.

Professor Fergus Gleeson, Chief Investigator for the programme, said

“The novel linking of diagnostic technologies, patient outcomes and biomarkers using AI has the potential to make a real difference to how people with suspected lung cancer are investigated. By differentiating between cancers and non-cancers more accurately based on the initial CT scan and blood tests, we hope to remove the delay and possible harm caused by repeat scans and further invasive tests. If successful, this has the potential to reduce patient anxiety and diagnose cancers earlier to improve survival and save the NHS money.”

This programme builds on the National Consortium of Intelligent Medical Imaging (NCIMI) at the Big Data Institute in Oxford, one of five UK AI Centres of Excellence. The funding, delivered through UK Research and Innovation’s (UKRI’s) Industrial Strategy Challenge Fund, is part of over £13m government investment in ‘data to early diagnosis and precision medicine’ for the research, development and evaluation of integrated diagnostic solutions. UKRI is also partnering with Cancer Research UK, which is making up to a £3m contribution to the cancer-focused projects. The Oxford-led project is one of six awarded from this competition.

Science Minister, Amanda Solloway MP, said:

“Our brilliant scientists and researchers in Oxford are harnessing world-leading technologies, like AI, to tackle some of the most complex and chronic diseases that we face. Tragically, we know that one in two people in the UK will be diagnosed with some form of cancer during their lifetime. The University of Oxford project we are backing today will help ensure more lives are saved and improved by using state of the art technology to identify cancerous tumours in the lung earlier and more accurately.”

Dr Timor Kadir, Chief Science & Technology Officer at Optellum Ltd, commented:

“Three industry leaders – Roche, Optellum and GE – have joined their expertise in molecular diagnostics, imaging and AI to help diagnose and treat lung cancer patients at the earliest possible stage. The programme results will be integrated into Optellum’s AI-driven Clinical Decision Support platform that supports physicians in choosing the optimal diagnostic and treatment procedures for the right patient at the right time.”

Ben Newton, General Manager, Oncology, at GE Healthcare, said:

“We are very pleased to be working with the University of Oxford via the NCIMI project on this important lung cancer research. By extending our existing NCIMI data infrastructure and creating innovative AI solutions to spot comorbid pathologies, we aim to help identify lung diseases earlier in the UK.”

Geoff Twist, Managing Director UK and Ireland and Management Centre European Agents at Roche Diagnostics Ltd, said:

“We are thrilled with this funding award, because it gives us the opportunity to work towards ground-breaking innovation in early diagnosis and because working in partnership is vital to achieve success in the health system. By bringing together the collective knowledge and expertise of these academic, medical and industry partners, this project has the potential to impact patient care globally through new diagnostic solutions in lung cancer.”

Dr Jesme Fox, Medical Director of the Roy Castle Lung Cancer Foundation, said:

“The majority of our lung cancer patients are diagnosed too late for the disease to be cured. We know that we need to be diagnosing lung cancer at an earlier stage, through screening. This innovative project has the potential to revolutionise lung cancer screening, making it more efficient and most importantly, saving lives. Roy Castle Lung Cancer Foundation is delighted to support this Programme”

Professor Xin Lu, co-Director of the CRUK Oxford Centre and Director of the Oxford Centre for Early Cancer Detection, commented:

“I am delighted that this national multi-site collaborative programme will be led from Oxford by Fergus Gleeson. Involving a world-class team of academics, clinicians, local and global industry, and patient representatives, this research is hugely important for accelerating lung cancer detection.”

 

* The 10 NHS England Lung Health Check sites are:

  • North East and Cumbria Cancer Alliance – Newcastle Gateshead CCG
  • Greater Manchester Cancer Alliance – Tameside and Glossop CCG
  • Cheshire and Merseyside Cancer Alliance – Knowsley CCG and Halton CCG
  • Lancashire and South Cumbria Cancer Alliance – Blackburn with Darwen CCG and Blackpool CCG
  • West Yorkshire Cancer Alliance – North Kirklees CCG
  • South Yorkshire Cancer Alliance – Doncaster CCG
  • Humber, Coast and Vale Cancer Alliance – Hull CCG
  • East of England Cancer Alliance – Thurrock CCG and Luton CCG
  • East Midlands Cancer Alliance – Northamptonshire CCG and Mansfield and Ashfield CCG
  • Wessex Cancer Alliance – Southampton CCG

 

New start-up Base Genomics launches

 

About the technology

TET-assisted pyridine borane sequencing (TAPS) is a new method for measuring DNA methylation, a chemical modification on cytosine bases. DNA methylation has important regulatory roles in the cell but is frequently altered in cancer. These altered DNA methylation levels are preserved in DNA that is released into the blood from cancer cells and therefore DNA methylation has great potential as the basis for a multi-cancer blood test. However, a key limitation to achieving this aim, especially for detecting cancer at the earliest stages, is the low sensitivity of current DNA methylation technology.

One of the advantages of TAPS over the current standard methodology is the avoidance of the use of bisulphite, a harsh chemical that severely degrades DNA. TAPS is a mild reaction that preserves DNA integrity and is effective at very low DNA concentrations, which would increase the sensitivity of blood-based DNA methylation assays. TAPS also better retains sequence complexity, enabling simultaneous collection of DNA methylation and genetic data, and cutting sequencing costs in half. Read more about the potential of TAPS as the basis for a multi-cancer blood test here.

The company Base Genomics has been launched to set a new gold standard in DNA methylation detection using this TAPS technology.

 

“I am thrilled about the launch of Base Genomics and look forward to seeing the TAPS technology developed in my lab applied to new technologies for cancer detection and the advancement of a variety of fields of biomedical research,”

Dr Chunxiao Song, assistant member of the Ludwig Institute Oxford Branch, co-founder of Base Genomics, chemistry advisor to the company.

 

 “Genomic technologies with the power, simplicity and broad applicability of TAPS come along very infrequently,

“It has the potential to have an impact on epigenetics similar to that which Illumina’s SBS chemistry had on Next Generation Sequencing.”

Base Genomics CTO Dr Vincent Smith.

 

About Base Genomics

Base Genomics has a team of leading scientists and clinicians, including Dr Vincent Smith, a world-leader in genomic product development and former Illumina VP; Professor Anna Schuh, Head of Molecular Diagnostics at the University of Oxford and Principal Investigator on over 30 clinical trials; Drs Chunxiao Song and Yibin Liu, co-inventors of TAPS at the Ludwig Institute for Cancer Research, Oxford; and Oliver Waterhouse, previously an Entrepreneur in Residence at Oxford Sciences Innovation and founding team member at Zinc VC.

The company has closed an oversubscribed seed funding round of $11 million USD (£9 million GBP), led by Oxford Sciences Innovation alongside investors with industry expertise in genomics and oncology. This funding will progress development of the TAPS technology, initially focusing on developing a blood test for early-stage cancer and minimal residual disease.

 

”The ability to sequence a large amount of high-quality epigenetic information from a simple blood test could unlock a new era of preventative medicine,

“In the future, individuals will not just be sequenced once to determine their largely static genetic code, but will be sequenced repeatedly over time to track dynamic epigenetic changes caused by age, lifestyle, and disease.”

Base Genomics founder and CEO Oliver Waterhouse.

 

“In order to realise the potential of liquid biopsies for clinically meaningful diagnosis and monitoring, sensitive detection and precise quantification of circulating tumour DNA is paramount,

“Current approaches are not fit for purpose to achieve this, but Base Genomics has developed a game-changing technology which has the potential to make the sensitivity of liquid biopsies a problem of the past.”

Base Genomics CMO Professor Anna Schuh

 

For more information, see the Base Genomics press release.

 

Study sheds light on risks of breast cancer after pre-invasive disease

Women who are diagnosed with ductal carcinoma in situ (DCIS) during breast screening go on to experience higher risks of developing breast cancer and of death from breast cancer, compared with the general population, according to new research published by The BMJ today. The risks were more than double those of the general population, even for women diagnosed with low or intermediate grade DCIS, and lasted until at least 20 years after diagnosis.

DCIS is a disease where malignant breast cells are found but have not spread beyond the milk ducts.

Diagnoses of DCIS have increased substantially in recent years, especially among women attending breast screening programmes. DCIS isn’t immediately life-threatening and does usually have a good prognosis, but it can increase the risk of developing an invasive breast cancer later on. The extent of this extra risk is uncertain.

So, researchers at the Nuffield Department of Population Health and Public Health England set out to evaluate the long term risks of invasive breast cancer and of death from breast cancer after DCIS diagnosed through breast screening.

Their findings are based on data from 35,024 women in England diagnosed as having DCIS by the NHS Breast Screening Programme from its start in 1988 until March 2014. They compared rates of invasive breast cancer and of death from breast cancer with the corresponding national rates for women of the same age in the same calendar year.

The researchers found that by December 2014, 2,076 women had developed invasive breast cancer, an incidence rate of 8.82 per 1,000 per year and more than double the number expected from national rates. In the same group of women, 310 died from breast cancer, a death rate of 1.26 per 1,000 per year and 70% more than expected from national rates.

For both invasive breast cancer and death from breast cancer, the increases continued for at least two decades.

The results also suggest that women who had more intensive treatment, such as a mastectomy, had a lower long term risk of invasive breast cancer than those who had breast conserving surgery, even when radiotherapy was given.

Professor Sarah Darby from the Nuffield Department of Population Health, who led the research, said ‘This is the first time we have been able to show that women with DCIS have more than double the risk of developing invasive breast cancer and dying from the disease, even up to 20 years after being diagnosed.

‘While this is concerning, understanding more about this risk puts us in a better position to make informed decisions about how to treat and monitor women with DCIS to give them the best possible care and save lives.’

The researchers point out that, at the moment, surveillance of women after a diagnosis of DCIS focuses just on the first few years. In the UK, for example, most women are recalled for yearly surveillance mammograms for five years, after which further follow-up is every three years via the national screening programme up to age 70 years.

Further studies are needed to build on these findings, in particular to try to work out which type of DCIS is most closely linked to the development of invasive breast cancer. This may have implications for follow-up and the frequency of surveillance imaging.

Funding was provided by Cancer Research UK, the National Institute for Health Research Oxford Biomedical Research Centre, and the UK Medical Research Council.