Department for BioMedical Research (DBMR)

DBMR Reserach Conference

The Effect of Hypoxia on the Genomic Architecture of Human Tumours

Monday, 2021/05/03, 17:00

Event organizer: Department for BioMedical Research
Speaker: Prof. Dr. Robert Bristow, Manchester Cancer Research Centre, The University of Manchester, Manchester, UK
Date: 2021/05/03
Time: 17:00 - 18:00
Locality: Zoom area
Murtenstrasse 35
3008 Bern
Characteristics: open to the public
free of charge

Bio Professor Robert Bristow joined the University of Manchester as Director of the Manchester Cancer Research Centre (MCRC) in August 2017 with a remit to developing a new cancer strategy for Manchester with a cancer team science approach. The MCRC is a unique partnership between Cancer Research UK, The University of Manchester and the Christie NHS Foundation Trust.
His primary research interests are in tumour hypoxia, DNA damage signalling and repair in tumours, and the genomics of prostate cancer progression and cancer treatment response. He is particularly interested in novel clinical trials that intensify cancer therapy to prostate cancer patients whose tumours harbour aggressive genetic changes and hypoxic sub-regions.
Professor Bristow is currently a senior group leader in Translational Oncogenomics at the CRUK Manchester Institute and was the lead PI for the Canadian component of the ICGC whole genome prostate cancer sequencing project (CPC-GENE).
He has served on a number of senior Scientific Advisory Boards and committees for: Prostate Cancer Foundation (USA), the MOVEMBER Foundation, the American Association for Cancer Research (AACR), the German Cancer Centre, Tuebingen Comprehensive Cancer Centre, NKI Amsterdam, the Danish Cancer Society and sits on the Scientific Executive Board for Cancer Research UK (CRUK). He has over 280 published papers and book chapters and is twice a Canadian Foundation for Innovation (CFI) awardee. He was made a Canadian Cancer Society Research Scientist in 2004, an ESTRO Honorary Fellow in 2011 and a Fellow of the Academy of Sciences (UK) in 2019.

Abstract Understanding the mechanistic basis for transition to late stage aggressive disease is vital for both assigning patient risk status in the localised setting and also identifying novel treatment strategies to prevent progression. Subregions of intratumoral hypoxia are found in all solid tumours and are associated with many biologic drivers of tumour progression. Crucially, more recent findings show the co-presence of hypoxia and genomic instability can confer a uniquely adverse prognosis. In-depth informatic and functional studies suggest a role for hypoxia in co-operating with oncogenic drivers (e.g. loss of PTEN) and suppressing DNA repair capacity to alter clonal adaption and evolution and driving an aggressive mutator phenotype. More specifically, hypoxic suppression of homologous recombination represents a "contextual lethal" vulnerability in hypoxic prostate tumours which could extend the application of existing DNA repair targeting agents such as poly-ADP ribose polymerase inhibitors. Further investigation is now required to assess this relationship on the background of existing genomic alterations relevant to prostate and other cancers, and also characterise the role of hypoxia in driving early metastatic spread.

Website: Prof. Dr. Robert Bristow, Manchester Cancer Research Centre, The University of Manchester, Manchester, UK

Host: PD Dr. phil. nat. Michaela Medova, Groupleader Radiation Oncology, Department for BioMedical Research, Inselspital Bern and University of Bern