Research into hypoxia (low oxygen) signalling pathways has revealed transcriptional systems that directly activate thousands of genes in hypoxic cells. Indirect actions of systems that respond to these genes massively amplify these responses to hypoxia. In cancer these pathways are dysregulated, both by oncogenic mutations and by the micro-environmental hypoxia that frequently develops in solid tumours. The lecture will consider the implications of ‘switching’ massively interconnected hypoxia pathways during cancer development. It will review evidence that individual components of hypoxia signalling pathways are highly heterogeneous in their effects on cancer growth, involving both pro- and anti-tumourigenic effects and consider the implications of selective pressures operating at multiple points to ‘tune’ interconnected pathways to enhance overall oncogenic drive.
Sir Peter Ratcliffe grew up in north Lancashire and won an open scholarship to study medicine at Gonville and Caius College, Cambridge. He undertook clinical training at St. Bartholomew’s Hospital, London, and after series of posts at the London postgraduate hospitals, moved to Oxford to train in nephrology. In 1990 he obtained a Wellcome Trust Senior Fellowship to work on cellular responses to hypoxia, retrained in molecular biology and founded a new laboratory working on hypoxia biology in cancer and circulatory diseases. He was appointed Nuffield Professor and Head of the Nuffield Department of Clinical Medicine in 2003, a position he held until 2016. He is currently Director of the Target Discovery Institute, and a Distinguished Scholar of the Ludwig Institute for Cancer Research. He is a Fellow of the Royal Society and the Academy of Medical Sciences and is an honorary member of the American Academy of Arts and Sciences. In the 2014 New Year’s Honours List, he was knighted for services to clinical medicine. His work was recognised by the award of the Nobel Prize for Physiology or Medicine 2019.
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