Understanding how DNA damage can lead to breast cancer development

Start Year: 2011
Finish Year: 2015
Chief Investigator: Dr Elizabeth Caldon
Grant Type: Postdoctoral Fellowship
Institution: Garvan Institute of Medical Research

Postdoctoral Training Fellowship

Thirty percent of breast cancers remain resistant to current biological therapies. This includes ‘basal-like’ breast cancers and cancers of women with defects in the familial breast cancer gene, Brca1. These tumours are characterised by a fast growth rate and an inability to effectively repair damage to their DNA.

Dr Caldon hypothesises that these processes are intrinsically linked. Excessive DNA synthesis in cells that cannot repair their DNA will result in the accumulation of more DNA errors and resultant genomic instability, which are driving forces in tumour progression. In particular, Dr Caldon hypothesises that the pro-proliferative cyclin proteins can assist in both driving cell proliferation and allowing the accumulation of DNA errors.

This study aims to confirm preliminary data showing that high expression of cyclin proteins can help evade the normal cellular response to DNA damage. Furthermore, these cyclin proteins appear to be directly regulated by DNA damage response pathways, which further links abnormal cell proliferation and DNA damage. By characterising the links between proliferation and DNA damage, Dr Caldon aims to develop tailored therapeutic strategies for women whose tumours present with defects in these processes.

This research is co-funded by NBCF and Cure Cancer Australia Foundation.