
Prof. Jinbin Xu
Washington University School of Medicine, USA
Title: Radiotracers for Imaging Oxidative DNA Stress in Cancer
Abstract:
Cancer cells consume a large amount of oxygen to produce energy to
maintain their proliferative status and require a constant supply of new DNA.
Nuclear bases made in cancer cells for DNA replication are under oxidative
stress and tend to be damaged much more frequently than those found in normal
cells. Dysfunctional redox regulation and increased reactive oxygen species
(ROS) in cancer cells cause oxidative damage either directly or indirectly to
DNA. Upregulation of MTH1, an oxidized purine nucleoside triphosphatase that
specifically hydrolyzes oxidized purine nucleoside triphosphates, occurs in various
cancers to repair oxidized DNA and suppress the accumulation of oxidatively
damaged nucleic acids. ROS causes cellular dysfunctions such as cell death and
mutagenesis by exerting oxidative damage to lipids, proteins, and nucleic acids
in living cells. Oxidative damage to nucleic acids can potentially alter
nuclear and mitochondrial DNA. In vivo measures of these processes could
provide a critical metric of disease progression and a target for drug
engagement. MTH1 has been reported to be a crucial enzyme in cancer
proliferation and resistance to cancer therapy. This talk will highlight the development
and validation of MTH1 radiotracers for imaging oxidative DNA stress in cancer.
Biography: