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.