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On 28-29th April 2021, we heard the latest developments from international leaders in these fields from the University of Oxford, Ludwig Cancer Research and beyond.

The Ludwig-Oxford Symposium on Cancer Early Detection and Epigenetics was co-hosted by Ludwig Cancer Research, the Cancer Research UK Oxford Centre and the Oxford Centre for Early Cancer Detection (OxCODE) on Wednesday 28th and Thursday 29th April 2021. Over 400 people joined for an exciting programme of talks on the recent advancements in cancer early detection and cancer epigenetics research.

In the welcome address, Chi Van Dang (Ludwig Cancer Research, Scientific Director) emphasised how these linked research fields hold great promise to alleviate the burden of cancer worldwide. Ludwig Oxford and OxCODE Director, Xin Lu shared her hope that this event would facilitate the exchange of ideas to inspire new collaborations to advance our understanding of cancer and improve its diagnosis and care. In the final welcome message, Tim Elliott (CRUK Oxford Centre, co-Director) highlighted the importance of multidisciplinary teams to address clinically relevant research questions, with events such as the Ludwig-Oxford Symposium important for sharing and integrating our efforts and strengthening partnerships around priorities such as early cancer detection.

Session 1 – Early Detection Technologies I

In the first session on Early Detection Technologies, chaired by Bethan Psaila (Weatherall Institute of Molecular Medicine and Radcliffe Department of Medicine, Oxford), Chunxiao Song (Ludwig Oxford) gave an introduction to his TAPS method for simultaneous genetic and epigenetic (DNA methylation) analysis. He shared his latest data on detecting liver and pancreatic cancers using DNA shed into the bloodstream. Following this, Nickolas Papadopoulos (Ludwig Cancer Research, Johns Hopkins School of Medicine) discussed the capabilities and limitations of the multi-cancer liquid biopsy test CancerSEEK. He revealed the findings of the DETECT-A trial that evaluated the ability of CancerSEEK to detect undiagnosed cancers in nearly 10,000 enrolled women.

Switching to imaging technologies, Jens Rittscher (Ludwig Oxford and Institute of Biomedical Engineering) noted the importance of multidisciplinary contributions to his team’s development of a computer-aided endoscopy analysis system for the identification and measurement of Barrett’s Oesophagus. Finishing the first session, Sangeeta Bhatia (Ludwig Cancer Research, Massachusetts Institute of Technology) described her exciting research using synthetic nanosensor probes that act as a readout of protease dysregulation to detect and monitor cancer.

Session 2 – Risk Stratification for Early Detection

The second session on Risk Stratification for Early Detection, chaired by David Hunter ((Nuffield Department of Population Health and Big Data Institute, Oxford), featured Ellie Barnes (Nuffield Department of Medicine, Oxford) who gave an overview of the DeLIVER programme for the earlier detection of hepatocellular liver cancer. Naomi Allen (Nuffield Department of Population Health and Big Data Institute, Oxford) outlined how UK Biobank data, including multi-omics and clinical imaging, can be used for early cancer detection research. Gillian Reeves (Nuffield Department of Population Health, Oxford) described her work within the Million Women Study for improving breast cancer risk stratification models beyond age and family history for potentially more targeted screening interventions in the future.

In wrapping up the first day, David Hunter summarised how the advancements in detection technologies combined with risk stratification studies will enable us to focus more on people who are at higher risk of developing cancer, with great promise for optimising benefit versus risk for cancer detection programmes in the future.

Session 3 – Cancer Epigenetics I

On the second day, the theme shifted to cancer epigenetics. In the session chaired by Natalia Gromak (Dunn School of Pathology, Oxford), Tony Kouzarides (University of Cambridge) shared his recent work identifying RNA modifying enzymes in AML-leukaemia, lung and pancreatic cancer, and developing drugs against them. Stephen B. Baylin (Ludwig Cancer Research, Johns Hopkins School of Medicine) discussed how chronic inflammation induces epigenetic changes in the genome that drive cancer initiation and the potential relevance of these findings to cancer prevention and therapy.

Session 4 – Early Detection Technologies II

Chunxiao Song (Ludwig Oxford) chaired the penultimate session focused on the interface of cancer epigenetics and cancer detection. Chuan He (Ludwig Cancer Research, University of Chicago) presented his lab’s genomic mapping of 5-hydroxymethylcytosine across 19 human tissues and their work on epigenetic mapping of DNA shed by tumours into blood for early cancer diagnosis, prognosis and treatment stratification. Kenneth W. Kinzler (Ludwig Cancer Research, Johns Hopkins School of Medicine) discussed the utility and limitations of methods for detecting circulating tumour DNA (ctDNA) and presented an approach that boosts sensitivity and specificity of ctDNA detection in minimal residual disease.

Session 5 – Cancer Epigenetics II

Yang Shi (Ludwig Oxford) kicked off the last session of the event, chaired by Skirmantas Kriaucionis (Ludwig Oxford), with his talk on the epigenetic mechanisms that control tumour responses to immunotherapy and his lab’s recent work harnessing those insights to develop new approaches to improving the efficacy of checkpoint blockade therapy. Nada Jabado (McGill University) described the effect of histone H3.3 glycine 34 to arginine/valine mutations on PDGFRA mutations, brain development and chromatin structure in glioma. Shelley Berger (University of Pennsylvania) shared her lab’s latest work on the transcription factor and tumour suppressor p53 and its role in re-locating p53 target genes to nuclear speckles to boost gene expression, with potential to impact on cancer development.

 

The Symposium was highly instructive and it was invigorating to hear from the forefront of cancer epigenetics and early cancer detection research. Our understanding of cancer epigenetics has become rich over time but now we need to effectively deploy this understanding to intercept cancer development and to reduce therapeutic resistance by making chemoradiation and immunotherapy more efficacious. The task in front of us requires our herculean team effort so I hope that the Symposium was not only stimulating but stimulates collaboration and new friendships as we join together to eliminate the suffering of cancer. - Chi Van Dang, Ludwig Cancer Research Scientific Director.

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