QResearch researchers collaborate on two major cancer projects

The Department of Primary Care and Health Sciences recently announced that researchers in the Primary Care Epidemiology Group are joining two landmark projects to combine healthcare data and artificial intelligence to improve cancer diagnosis.

Led by Professor Julia Hippisley-Cox, the team will utilise the QResearch database of routinely collected electronic patient health records for studies on lung and oesophageal cancer diagnosis.

The two projects, announced today as part of a £13m investment from UKRI through their industrial strategy challenge fund, brings together different strengths from academia, charities, digital health and diagnostics companies.

Both projects are part-funded by Cancer Research UK.

DELTA, led by the University of Cambridge, will help to diagnose oesophageal cancer, which has increased 6-fold since the 1990s. Just 15% of people will survive for 5 years or more – often because it’s diagnosed too late.

Barrett’s oesophagus, a condition that can turn into cancer of the oesophagus, is more common in patients who suffer with heartburn. By using a new test for patients with heartburn, called the ‘Cytosponge’, the project aims to diagnose up to 50% of cases of oesophageal cancer earlier, leading to improvements in survival, quality of life and economic benefits for the NHS.

Professor Hippisley-Cox’s team are leading on the clinical epidemiology element of this research programme. The researchers will interrogate the QResearch database with the aim of developing a risk prediction algorithm that will be able to identify those individuals at highest risk of oesophageal cancer for further investigation.

DART (The Integration and Analysis of Data Using Artificial Intelligence to Improve Patient Outcomes with Thoracic Diseases), led by the University of Oxford, will accelerate lung cancer diagnosis, increasing the likelihood that treatment will be successful. See the full story on this announcement here.

Academics, NHS clinicians, the Roy Castle Lung Cancer Foundation and industrial partners (Roche Diagnostics, GE Healthcare, Optellum) will work with the NHS England Lung Health Checks programme to combine clinical, imaging and molecular data for the first time using artificial intelligence algorithms.

Professor Hippisley-Cox’s team 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. Find out more about this project here.

The QResearch database is one of the largest clinical research databases in Europe, covering 35 million patients from 1,500 GP practices throughout the UK. It includes longitudinal data collected over 25 years that is linked at an individual patient level to Hospital Episode Statistics (HES), mortality data and cancer registration (more details here), making it an extremely rich resource for cancer research.

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

 

Yang Shi joins the Oxford Cancer community

Yang Shi, who joins Ludwig from Harvard University, is a world leader in the field of epigenetics, which explores how chemical modifications to chromatin—the combination of DNA and histone proteins—control the organisation and expression of the human genome. Aberrations in those processes are vital drivers of cancer and underlie many other diseases and disorders.

“Yang has an outstanding track-record of innovative research into the identity and mechanisms of action of chromatin modifiers. We are delighted that Yang is bringing his wealth of experience, international standing and collaborative spirit to lead our cancer epigenetics theme at Ludwig Oxford.”

~ Xin Lu, Director of the Ludwig Oxford Branch.

Shi is widely known for his discoveries regarding a chemical modification, methylation, made to the histone proteins. In 2004, Shi and his colleagues identified and characterised an enzyme, LSD1, that erases methyl marks from histones. Their discovery upended a 40-year-old dogma that considered such modifications irreversible, altering longstanding models of genomic regulation. Shi’s laboratory went on to identify many other histone demethylating enzymes with roles in a diverse array of biological processes. More recently, his group discovered several enzymes that methylate RNA and possibly influence the translation of gene transcripts into proteins.

Shi is applying these fundamental discoveries to the benefit of patients. His group’s work on LSD1 led to the development of LSD1-inhibitors now in clinical trials for the treatment of cancer. More recently, Shi and his colleagues demonstrated that inhibiting LSD1 might also help make otherwise non-responsive tumours susceptible to the checkpoint blockade immunotherapy. His lab is additionally studying the role and therapeutic manipulation of epigenetic modifiers in pediatric high-grade gliomas and acute myeloid leukaemia.

“Yang’s science is of the highest calibre—as rigorous and collaborative as it is original—and we are very excited to have him in the Ludwig community. I’m sure many of our researchers will benefit from his expertise, and that they will be equally generous with their own expertise and support as he explores the implications of his discoveries for cancer biology and the design of new therapies.”

~ Chi Van Dang, Scientific Director of the Ludwig Institute.

Shi obtained his PhD from New York University, completed his postdoctoral training with Thomas Shenk of Princeton University and joined the faculty of Harvard Medical School in 1991, where he was most recently C.H. Waddington Professor of Pediatrics. Shi has received many honours for his contributions to epigenetics and is a fellow of the American Association for the Advancement of Science and a member of the American Academy of Arts and Sciences.

Find out more about Yang’s research.

Power of the patient voice

Clinical trial research from Prof Sarah Blagden, Department of Oncology, was recently published in Lancet Oncology. This work was conducted as part of the larger ICON8 ovarian cancer study and found that ovarian cancer patients placed on a more-frequent chemotherapy treatment plan have the same survival rates but poorer quality of life than those receiving the standard, less-frequent treatment.

Chemotherapy can cause significant side effects which can impact on the day-to-day functioning of patients. Some of these are not necessarily definable symptoms but manifest in changes to their Quality of Life (QOL) – such as the ability to work or take part in family life.

QOL is of particular importance to cancer patients, especially those with advanced or terminal cancers. Investigators are increasingly encouraged to include measures of QOL, via specific questionnaires, into their clinical studies but it is often measured poorly (using the wrong questions or too infrequently).

ICON8 was a phase III clinical trial that randomised 1,540 patients with advanced epithelial ovarian cancer to three different chemotherapy regimens. Those in one arm received chemotherapy once every three weeks (the current standard treatment), whilst patients in the other two arms received chemotherapy weekly.

Although the study showed patients in the thee arms had the same survival outcome, suggesting the weekly or 3-weekly treatments were equivocal, the QOL analysis gave a very different picture. It showed that patients who on the weekly treatments had more fatigue and longer-lasting nerve damage.  Sarah’s research concluded that the 3 weekly (standard) treatment was more tolerable for ovarian cancer patients and the different treatments were not equivocal after all.

Sarah Blagden, Associate Professor says;

To me, this study highlights how important it is to include the patients’ experience as a readout in clinical trials. The patients and study centres were fantastic at ensuring the QOL questionnaires were filled in and collected, and the data were carefully analysed by the MRC Trials team at UCL. The results completely changed our interpretation of the data. Not only that, but we can now confidently tell patients starting this treatment in the future what their experience is likely to be.

Whilst survival rates are often prioritised over QOL when interpreting study results, QOL is an important factor to consider when weighing up the benefits of one treatment over another. Patients and their wellbeing need to be at the forefront of this decision-making process.

To read more about this paper see here.

This research was funded by Cancer Research UK, Medical Research Council, Health Research Board Ireland, Irish Cancer Society and Cancer Australia.

Virtual Annual Cancer Symposium 2020

Registration is now open for the CRUK Oxford Centre’s 9th Annual Symposium. It will take place virtually on Wednesday 21st October 2020.

This year’s event will be different – we unfortunately cannot host our event as planned due to COVID-19 pandemic. As a result, we are not able to showcase a poster competition and abstracts will not be submitted.

However, we will be hosting a 1 day online event, which will include:

  • themed talks ranging from Non-Genetic Heterogeneity to Early Detection
  • New to Oxford session, featuring new Oxford cancer researchers and insights into where Oxford research may be going
  • a special talk by our Keynote Prof. zur Hausen

Programme:

Details of the full programme is currently being confirmed – please keep an eye on our Eventbrite page or our dedicated symposium page for further updates

Registration:

Registration is free. Sign up here

Please note that registration is only open to Centre members. (Please use this link to become a Centre member.)

 

If you have any questions regarding the Symposium please contact the Centrecancercentre@oncology.ox.ac.uk

Affordable approaches to earlier cancer diagnosis in India

Dr Toral Gathani wins seed funding as part of Cancer Research UK’s Affordable Approaches to Cancer scheme

Drug target potential for myelofibrosis

A new paper led by Dr Bethan Psaila, from the Weatherall Institute of Molecular Medicine (WIMM) of the Radcliffe Department of Medicine, has revealed a potential new immunotherapy drug target in the treatment of myelofibrosis.

Myelofibrosis is an uncommon type of bone marrow cancer characterised by gene mutations acquired in blood stem cells that lead to over-production of bone marrow cells called megakaryocytes, development of scarring or ‘fibrosis’ that stops the bone marrow being able to produce blood cells in adequate numbers, low blood counts and a large spleen.

At present, bone marrow transplant is the only potentially curative treatment for myelofibrosis, but this procedure carries high risks and only a small proportion of patients are suitable candidates for this. While drug therapies including JAK inhibitors can improve symptoms and quality of life, none are curative and these do not improve the bone marrow fibrosis. Therefore, there is a need to identify new targets for therapeutic development.

In a paper recently published in Molecular Cell, Beth Psaila and her team investigated a specific aspect of myelofibrosis, which is an increased frequency of bone marrow megakaryocyte (MK) cells. MKs are the bone marrow cell responsible for the production of platelets. While they are rare cells in healthy bone marrow, a pathogenomic feature of myelofibrosis is that they are observed in high numbers, and they are recognised as the key cellular drivers of fibrosis.

In order to better understand the cellular and molecular pathways leading to over-production of Mks and their dysfunction, the team used single-cell analyses, studying over 120,000 blood stem/progenitor cells individually.

This led to two key observations: firstly, that the proportion of blood stem cells that were genetically ‘primed’ to give rise to MKs was 11-fold higher in myelofibrosis patients than in healthy donors, and secondly that MK genes were being switched on even in the most primitive stem cells in myelofibrosis, suggesting massive expansion of a ‘direct’ route for MKs to develop from stem cells in myelofibrosis, a phenomenon that was almost undetectable in healthy bone marrow.

They found that the myelofibrosis stem/progenitor cells, but not the wild-type or normal stem cells, expressed a high level of G6B, a immunoglobulin cell-surface receptor protein. They validated G6B as an exciting potential immunotherapy target that might be utilised to specifically ablate both the cancer stem cell clone and the fibrosis-driving MK cells.

Dr Beth Psaila commented:

“The finding that G6B is markedly increased in the cancer stem cells is very important, as it suggests that targeting G6B in combination with a stem cell marker may be a way of selectively targeting the cancer-driving stem cells while sparing healthy stem cells.

“Identifying ways to knock out the disease-initiating cells is crucial to make progress in this disease, as currently there are no curative treatments available to offer the majority of our patients.”

Going forward, Beth and her team will be working on further validating their targeting strategy to see if it might be translated to the clinic.

About Beth

Beth is a CRUK Advanced Clinician Scientist at the MRC Weatherall Institute of Molecular Medicine. The primary focus of her group is on megakaryocyte and platelet biology in cancer, and the application of single-cell approaches to clarify the cellular pathways by which megakaryocytes arise from haematopoietic stem cells.

She trained at Clare College, Cambridge, Imperial College London/The Hammersmith Hospital, Cornell, New York, and the National Institutes of Health, Bethesda USA, Beth is also an Honorary Consultant in Haematology in Oxford and a Senior Fellow in Medicine of New College, Oxford.

This research was conducted in collaboration with Prof Adam Mead and Dr Supat Thongjuea in the WIMM, including using data that was generated by Dr Alba Rodriguez-Meira. The work was partially funded by a Cancer Research UK Advanced Clinician Scientist Fellowship, a CRUK Innovation Award; a Wellcome Career Development Fellowship and a Medical Research Council (MRC) Senior Clinical Fellowship.

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.

 

Oxford joins cancer coronavirus registry project

Oncologists at the University of Oxford have joined with researchers at the University of Leeds and Birmingham to help monitor cancer patients who have tested positive for COVID-19.

The purpose of the UK Coronavirus Cancer Monitoring scheme is to assess how cancer patients will be impacted by the coronavirus outbreak and help to make informed treatment pathways through clinician-lead reports. In doing so, it is hoped that the monitoring system will ensure that high-quality cancer care is being delivered in order to safeguard patients during this time.

There are many unknowns in terms of the interactions between COVID-19 and cancer, including disease-specific mortality such as which type of cancer patients are at risk, age-specific cancer mortality such as how older cancer patients will cope with coronavirus infection, interaction with cancer treatments and who is most at risk in terms of treatment, impact of public health interventions and potential impact on patients.

Oxford will contribute to the project by collecting information to submit to a database, which tracks the prevalence of COVID-19 infections with associated anonymised data about the site of disease and mortality. This will be achieved through a newly-formed network of cancer COVID-19 response reporting clinicians, covering 82% of the UK’s cancer centre network.

In return, the scheme will relay daily updates back to the Oxford cancer centres and help to inform key decisions for patients who are at-risk.

The project team is made up of medical oncologists, data scientists and graphic designers including the University of Oxford, University of Birmingham, University of Leeds, Kings College London, The Clatterbridge Cancer Centre, University College London and Edinburgh Cancer Hospital. This work is supported by the Oxford Biomedical Research Centre.

Oxford technology holds great promise for a multi-cancer blood test

Ongoing Oxford research aims to improve the sensitivity of cancer blood tests with the goal of earlier detection for a variety of cancers.