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.