Sydney West Translational Cancer Research Centre
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A/Prof Vincent Murray:The molecular biology of the cancer chemotherapeutic agents, Cisplatin and Bleomycin



Rountree Room 356, Level 3, Biological Sciences Building D26, UNSW

How do cancer chemotherapeutic agents work?

Cisplatin and bleomycin are anti-tumour agents that are utilised to treat testicular, ovarian and other cancers. The introduction of cisplatin raised the cure rate for testicular cancer to over 90%. This seminar will discuss why cisplatin and bleomycin are successful anti-tumour agents. In particular the interaction of cisplatin and bleomycin with DNA will be discussed and how this is important for their mechanism of action.

The research aim of Vincent Murray's laboratory is to use the methodology of molecular biology to investigate the mechanism of action of anti-tumour agents. He has concentrated on two cancer chemotherapeutic agents, cisplatin and bleomycin. Murray's laboratory has recently developed two important techniques for the investigation of the interaction of anti-tumour drugs with DNA. In the first technique, the capillary electrophoresis capabilities of automated DNA sequencers were exploited to determine the DNA sequence specificity of DNA damaging agents. This technique has higher resolution, greater sensitivity and is easier to perform than previous methods. This technique can be utilised to examine the DNA sequence specificity in both purified DNA sequences and also in human cellular DNA. In the second technique, the power of next generation DNA sequencing was utilised to determine the sites of DNA cleavage at the nucleotide level for the entire human genome in human cells for the anti-tumour drug, bleomycin,. This was the first occasion that the genome-wide pattern of DNA cleavage was determined at base pair resolution for an anti-cancer drug. This latter technique enables a more detailed evaluation of the human genomic sites damaged by bleomycin and provided insights into its mechanism of action.