Oxford | Emerson Collective Cancer Research Fund

We are delighted to announce a new funding scheme for innovative cancer research, through generous support from the Emerson Collective. Applications will be invited in early January 2019, but in preparation for this we are advising you now of this upcoming opportunity. The Oxford | Emerson Collective Cancer Research Fund will request individual or team proposals for research projects related, but not limited to, immunotherapy, metabolic therapies, early detection advancements, ‘high risk/high reward’ initiatives and/or -omic approaches cancer and drug development. Positive criteria include the potential of a project to significantly impact our understanding of and/or approaches to the prevention, diagnosis, or treatment of cancer.

 

Criteria

This Funding Scheme will be open to all faculty undertaking research relevant to cancer at the University of Oxford.

A team of Oxford | Emerson Collective Cancer Research Fund employees and associates will evaluate the applicant pool.

Applicants will be evaluated on the following positive criteria:

  • The audacity and innovation of the research proposal. Incremental research will not be funded.
  • The potential of the proposed research to affect multiple cancer types
  • The potential to translate said research into further experiments, and clinical trials
  • The applicant’s lack of resources to pursue the proposed research
  • Compliance with a two-year maximum timeframe for research

 

The applicant’s prior experimental track record will not be the principal determining factor in evaluation.

 

Timeline

Scheme opens for applications in early January.

Proposals due: March 8, 2019 at 5 p.m EST (see proposal submission guidelines below).

Funding available early May 2019. Post-award follow-up will entail 12- and 24- month progress and financial reports.

 

Amount of Funding

  • Awards range from £50,000 up to £200,000 for up to 2 years for both direct and indirect costs.
  • You may apply for additional funding for the same projects on subsequent RFP rounds, though new projects will be prioritized.
  • This fund does not support incremental research.
  • Funding is available to support personnel, supplies, equipment, and other general costs associated with the project. Provide a categorical budget outline for the project, see budget template for details. Indirect costs may total 15% maximum. It applies to the project costs and should be included in your budget request. Total budget request including the indirect costs should not exceed £200K.
  • All proposed budgeting must conform to the general policies of the institution.

Questions? Please submit questions to  Claire Bloomfield, email: Claire.bloomfield@oncology.ox.ac.uk

 

Please do get in touch if you plan to submit, to discuss University requirements and protecting any sensitive information you may wish to share.

Further information available in the Oxford Emerson Announcement and Guidance.

Workshop “Concepts in Translational Cancer Research”

We are delighted to announce the opening of registration for the first Cancer Research UK Oxford Centre Concepts in Translational Cancer Research Workshop on February 7th 2019.

The aim of the workshop is to support Oxford researchers meet the increasing expectations from research funders to be able to clearly and credibly articulate a projects relation to clinical need.

Professors Ian Mills, Francesca Buffa, and Deborah Goberdhan, and the Oncology Clinical Trials Office are running this event targeted at students, post-docs and junior PI’s interested in finding out how to apply their fundamental research to cancer.

Attendees will have the opportunity to find out more about widely used tools and techniques in translational cancer research and take part in a breakout session where they will get the opportunity to discuss their project with a relevant expert.

If you have ever found yourself asking any of the below, please feel free complete the below application form and return to cancercentre@oncology.ox.ac.uk by December 21st 2018, to register.

  1. Are genes or pathways that form a focus of my research perturbed or mutated in particular cancers or subtypes of cancers?
  2. Can these genes or pathways stratify patient groups in a manner that predicts disease progression or treatment response?
  3. Can any of the biological processes that I am studying be affected by clinically approved drugs or drugs that are undergoing clinical trials?  If so, how might I access those drugs and use them in my model systems?
  4. If it is not easy to answer questions 1-3 then what are the datasets and who are the people that I need to interact with to address these questions?
  5. What models and tools should I use to study further study the role of my gene/pathway in cancer?

 

Please fill in the below application form and send it to us via cancercentre@oncology.ox.ac.uk.

Application form for “Concepts in Translational Cancer Research”

 

 

Please do not hesitate to get in touch with the Centre team if you have any questions or queries about the event (cancercentre@oncology.ox.ac.uk).

Dr Ross Chapman welcomed as EMBO Young Investigator

Member of the CRUK Oxford Centre and Wellcome Centre for Human Genetics researcher Dr Ross Chapman has been selected as one of the European Molecular Biology Organisation’s Young Investigators for 2018.

The EMBO Young Investigator Programme identifies recent group leaders with a proven record of scientific excellence and offers them access to a range of benefits during their four-year tenure. These include an award of 15,000 euros, with the potential for additional funding, mentorship by a senior scientist from the community of EMBO Members, access to training in leadership skills and responsible research practices, as well as networking opportunities.

Additional benefits provided by the Programme include the use of core facilities at the European Molecular Biology Laboratory in Heidelberg, Germany, and travel grants for the Young Investigators and their research groups to attend conferences.

“The accepted candidates have all shown outstanding promise in their early careers and impressed our selection committee with both the quality of their current work and their proposals for future research:” said EMBO Director, Maria Leptin. “We look forward to supporting them in establishing their own research groups.”

Dr Ross Chapman commented: “I’m thrilled for having been selected as an EMBO Young Investigator. It’s going to be great to interact with a community of young scientists involved in exciting and cutting-edge research. I’m also very grateful for the benefits its going to bring to my group. The EMBO young investigator programme comes with lots of opportunities for my team members to interact with scientists across Europe, and also allows them to apply for travel grants and receive training. Most importantly, this support from EMBO is aimed towards increasing the visibility of my group’s research, and this is also going to profit the whole team.”

The 2018 group of Young Investigators comprises scientists based in 11 countries, including two European Molecular Biology Conference (EMBC) Associate Member States: India and Singapore.

The next application deadline is 1 April 2019. More information is available at http://www.embo.org/funding-awards/young-investigators

 

 

Content adapted from: https://www.medsci.ox.ac.uk/news/dr-ross-chapman-welcomed-as-embo-young-investigator

New dual-action cancer-killing virus

Scientists have equipped a virus that kills carcinoma cells with a protein so it can also target and kill adjacent cells that are tricked into shielding the cancer from the immune system.

It is the first time that cancer-associated fibroblasts within solid tumours – healthy cells that are tricked into protecting the cancer from the immune system and supplying it with growth factors and nutrients – have been specifically targeted in this way.

The researchers, who were primarily funded by the MRC and Cancer Research UK, say that if further safety testing is successful, the dual-action virus – which they have tested in human cancer samples and in mice – could be tested in humans with carcinomas as early as next year.

Currently, any therapy that kills the ‘tricked’ fibroblast cells may also kill fibroblasts throughout the body – for example in the bone marrow and skin – causing toxicity.

In this study, published in the journal Cancer Research, the researchers used a virus called enadenotucirev, which is already in clinical trials for treating carcinomas. It has been bred to infect only cancer cells, leaving healthy cells alone.

They added genetic instructions into the virus that caused infected cancer cells to produce a protein called a bispecific T-cell engager.

The protein was designed to bind to two types of cells and stick them together. In this case, one end was targeted to bind to fibroblasts. The other end specifically stuck to T cells – a type of immune cell that is responsible for killing defective cells. This triggered the T cells to kill the attached fibroblasts.

Dr Joshua Freedman, from the Department of Oncology at the University of Oxford, who was first author on the study said: “We hijacked the virus’s machinery so the T-cell engager would be made only in infected cancer cells and nowhere else in the body. The T-cell engager molecule is so powerful that it can activate immune cells inside the tumour, which are being supressed by the cancer, to attack the fibroblasts.”

Dr Kerry Fisher, from the Department of Oncology at the University of Oxford, who led the research said: “Even when most of the cancer cells in a carcinoma are killed, fibroblasts can protect the residual cancer cells and help them to recover and flourish. Until now, there has not been any way to kill both cancer cells and the fibroblasts protecting them at the same time, without harming the rest of the body.

“Our new technique to simultaneously target the fibroblasts while killing cancer cells with the virus could be an important step towards reducing immune system suppression within carcinomas and should kick-start the normal immune process.

“These viruses are already undergoing trials in people, so we hope our modified virus will be moving towards clinical trials as early as next year to find out if it is safe and effective in people with cancer.”

The scientists successfully tested the therapy on fresh human cancer samples collected from consenting patients, including solid prostate cancer tumours which reflect the complex make-up of real tumours. They also tested the virus on samples of healthy human bone marrow and found it did not cause toxicity or inappropriate T cell activation.

Dr Nathan Richardson, head of molecular and cellular medicine at the MRC said: “Immunotherapy is emerging as an exciting new approach to treating cancers. This innovative viral delivery system, which targets both the cancer and surrounding protective tissue, could improve outcomes for patients whose cancers are resistant to current treatments. Further clinical studies will be crucial to determine that the stimulation of the patient’s immune system does not produce unintended consequences”.

Dr Michelle Lockley, Cancer Research UK’s expert on immunotherapy, said: “Using the power of the body’s own immune system to tackle cancer is a growing area of research. This work in human tumour samples is encouraging, but can be complicated – one of the biggest challenges of immunotherapies is predicting how well they will work with the patient’s immune system, and understanding what the side effects could be. The next stage will be using clinical trials to test whether this is both a safe and effective way to treat the disease in people.”

The virus targets carcinomas, which are the most common type of cancer and start in cells in the skin or in tissues that line or cover internal organs, such as the pancreas, colon, lungs, breasts, ovaries and prostate.

The study was funded by Cancer Research UK, the Medical Research Council, the Kay Kendall Leukaemia Fund and the Oxford NIHR Biomedical Research Centre. Materials were provided by PsiOxus Therapeutics Ltd.

 

 

 

Content adapted from the MRC website.

Transatlantic collaboration to support earlier detection of pancreatic and oesophageal cancer

Oxford researcher Chunxiao Song, who is a group leader and chemist at the Ludwig Institute for Cancer Research, recently gave an interview to CRUK speaking about his work recently funded by the CRUK-OHSU Project Award. The Award is jointly funded by CRUK and Oregon Health and Science University (OHSU).

In collaboration with Dr Thuy Ngo (OHSU) Chunxiao is developing novel tools to analyse liquid biopsies for pancreatic and oesophageal cancer. The aim is to use epigenetic and transcriptome technology to detect cancer earlier and provide information on where the cancer originated from. The researchers plan to use machine learning to create classification models that distinguish cancer patients from healthy controls.

The collaborating researchers believe that a combination of those two technologies will generate a fuller picture than a focus on just one technology. Chunxiao explains: “Our project uses liquid biopsies – a test that looks for DNA and RNA shed by tumours (and in fact all cells) in a patient’s blood sample. I have developed new measuring technologies that use less harsh chemicals than the standard approach. This causes less DNA degradation, which makes it easier to measure small quantities of cell -free DNA. Thuy has focused her research on measuring cell-free RNA. This is even more difficult than measuring cell-free DNA – but she has developed a special protocol that’s really gentle and doesn’t cause degradation of the RNA.”

Chunxiao also speaks about his experiences with applying for CRUK funded grants. He emphasises how uncomplicated the process is, and how well CRUK supports applicants: “My advice to anyone thinking of putting in an application is to contact the CRUK funding managers early on because they can help guide you through the process from the beginning.”

The full interview can be found via this link.

 

 

(Content adapted from www.cancerresearchuk.org)

Improving the Efficacy of Immune-therapies for Melanoma Patients

In his recent commentary “Long-term survival with anti-PD-1-based immunotherapy, but what is the best approach?” in the Lancet Oncology Prof. Middleton, Cancer Research UK Oxford Centre Co-Director and Head of the Department of Oncology at the University of Oxford, discusses how the clinical community should look to build on the already transformative use of immune therapies to treat patients with melanoma.

Having more than doubled life expectancies for late-stage metastatic melanoma patients, there still remains significant potential for improving how and when these novel therapeutics are deployed, for which patients they are prescribed, and how to limit the side effects of these agents. These questions form the focus of efforts of cancer researchers across Oxford,  from  fundamental laboratory based research to national collaborations, and to clinical trials that are improving the lives of patients treated at the Oxford University Hospitals Foundation Trust and across the UK.

 

Marseille-Oxford Cancer Centres Collaboration (MOC3)

 

October 4th and 5th 2018 saw the first Marseille-Oxford Cancer Centres Collaboration  (MOC3) meeting, held in the beautiful location of Villa Gaby, Marseille. The meeting was held to initiate a new partnership between the Cancer Research UK Oxford Centre, the Cancer Research Centre of Marseille and the Institut Paoli-Calmettes.

The objectives of these cancer centres are closely aligned, across both basic and clinical activities. The aim of MOC3 is to benefit from the complementary state-of the-art expertise and experimental and clinical infrastructures of the two sites to tackle major clinical challenges faced by those treating cancer patients.

The first meeting focussed on genome stability and the DNA damage response, based upon the respective strengths in these fields of both centres, from basic through translational research and in clinical practice. Thirty-five Oxford scientists and sixty-five Marseille scientists including students, post-doctoral fellows and group leaders attended the meeting which consisted of talks, posters sessions and a workshop – the latter proving very successful in identifying new collaborative projects that will be up-and-running in the next few months.

A follow-up meeting will take place in 2019 in Oxford and will be aimed at identifying collaborative projects centred around the DNA damage response and the maintenance of genome stability in relationship to leukemias and pancreatic cancer.

Metabolic profiles of breast cancer linked to response to metformin treatment

 

(B)(extract): Static PET-CT images in coronal plane pre- and post-metformin are from an individual with an

increase in KFDG-2cpt following metformin;note increased uptake in axillary lymph nodes (circled).

 

 

An international collaborative team of medical oncologists, radiologists, cell biologists and bioinformaticians led from Oxford by Simon Lord and Adrian Harris, have identified different metabolic response to metformin in breast tumours that link to change in a transcriptomic proliferation signature.

Published last week in Cell Metabolism, the team integrated tumour metabolomic and transcriptomic signatures with dynamic FDG PET imaging to profile the bioactivity of metformin in primary breast cancer.

Simon Lord stated: “This study shows how the integrated study of dynamic response to a short window of treatment can inform our understanding of drug bioactivity including mechanism of action and resistance. Further work will look to identify how mutations in mitochondria may define the metabolic response of tumours.”

The group demonstrated that metformin reduces the levels of several mitochondrial metabolites, activates multiple mitochondrial metabolic pathways, and increases 18-FDG flux in tumours.

The paper “Integrated pharmacodynamic analysis identifies two metabolic adaption pathways to metformin in breast cancer” defines two distinct metabolic signatures after metformin treatment, linked to mitochondrial metabolism. These differential metabolic signatures apparent in tumour biopsy samples, did not link to changes in systemic metabolic blood markers including insulin and glucose, suggesting metformin has a predominant direct effect on tumour cells. Analysis of the dynamic FDG-PET-CT data showed that this novel imaging technique may have potential to identify early response to treatment that is not apparent using standard static clinical FDG-PET-CT.

 

 

Key point summary of the study:

  • There is great interest in repurposing metformin, a diabetes drug, as a cancer treatment
  • Two distinct metabolic responses to metformin seen in primary breast cancer
  • Increased 18-FDG flux, a surrogate marker of glucose uptake, observed in primary breast tumours following metformin treatment
  • Multiple pathways associated with mitochondrial metabolism activated at the transcriptomic level
  • Further evidence that metformin’s predominant effects in breast cancer are driven by direct interaction with tumour mitochondria rather than its effects on ‘host’ glucose/insulin metabolism

 

The study has been funded by Cancer Research UK, the Engineering and Physical Sciences Research Council, the Medical Research Council, and the Breast Cancer Research Foundation.

 

The published paper can be found at:

https://www.cell.com/cell-metabolism/home

 

Content adapted from the original paper by Simon Lord et al.

AstraZeneca – Oxford Cancer Symposium (AZOCS), Thursday 13th September 2018 | Keble College, Oxford

 

AstraZeneca – Oxford Cancer Symposium (AZOCS)

Thursday 13th September 2018 | Keble College, Oxford

 

On Thursday 13th June, Keble College in Oxford hosted the
inaugural AstraZeneca – Oxford Cancer Symposium (AZOCS).

 

Over 125 researchers from Oxford and 90 cancer scientists from AstraZeneca and MedImmune attended to develop and establish a series of collaborative cancer research projects.

 

Almost 100 posters and 27 presentations showcased current
projects across all organisations, covering DNA Damage
Response
, Early-Phase Clinical Trials, Enabling Technologies,
Epigenetics, Immuno-Oncology, and Radiation Oncology.

 

 

David Andrews from AstraZeneca in Cambridge commented:

“The feedback I have had from AstraZeneca and Medimmune colleagues has been overwhelmingly positive and it is clear there are many opportunities for us to collaborate – from target identification and validation all the way through to patient studies. We are very excited by the prospect of deploying our disease know-how, target knowledge and
portfolio of drugs in development alongside Oxford’s excellent
access to patients and patient-derived models.
Oxford’s specific disease and biological knowledge should also
enable us to more deeply understand biological targets

and bring benefit to patients.”
 

 

Chris Schofield from the Department of Chemistry in Oxford
emphasised: “The AZ-Oxford meeting showcased brilliant
science from both organisations aimed at enabling breakthrough treatments for cancer. The truly impressive research ranged from fundamental work on the origins of tumorigenesis to clinical studies. There is clearly enormous potential for industry and academic to work synergistically to cement the UK’s leading position in cancer research.”

 

 

Poster winners for the AZOCS Poster Prizes 2018 are:

 

A Fluorescent Reporter of Base Editing

Activity Reveals Editing Characteristics of APOBEC3A
and APOBEC3B

– Matthew Coelho, AstraZeneca

A gene signature associated with PTEN activation defines good outcomes in intermediate-risk prostate cancer cases

– Chee Wee Ong, University of Oxford

 

 

If you attended the Symposium and would like to find out any more information about any of the presentations you saw, any of the posters, or further information on the CRUK Oxford Centre or AstraZeneca/MedImmune then please contact cancercentre@oncology.ox.ac.uk .

 

If you would like further information on how to download the Networking Meeting App ATTENDIFY, please contact cancercentre@oncology.ox.ac.uk .