- 17 October 2019
1:00 pm - 2:00 pm
THURSDAY 17 October 2019, 1.00 PM
Auditorium, Level 6, Bancroft Building
Exploiting chromosomal instability of cancer cells for therapeutic response
Professor Kum Kum Khanna
Signal Transduction Deputy Coordinator
QIMR Berghofer Medical Research Institute
Our research aims to uncover the vulnerabilities created by chromosomal instability (CIN) which refers to the acquisition of abnormal chromosome numbers or structures, in cancer cells. As a part of an NHMRC funded Program Grant we are interested in targeting Triple-negative breast cancer (TNBC), characterized by complex genomes, where little of their genomes remain at normal copy number which could be exploited for development of novel therapeutics. Currently, there are no targeted therapies available for TNBCs despite remarkable progress in targeted and immune-directed therapies for other solid organ malignancies. We have recently provided evidence for breast cancer subtype-specific differences in response to anti-mitotic drugs that is dependent on levels of Cep55, which allows a CIN permissive state (EMBO Mol Medicine 2018 Sep;10(9). pii: e8566). To decipher the mechanism by which Cep55 promotes CIN and tumorigenesis in vivo, we developed a novel “knock-in” transgenic mouse model that ubiquitously overexpresses Cep55 (Cep55Tg/Tg) and a knockout mouse model that deletes (Cep55-/-). These models demonstrate the importance of precise regulation of CEP55 levels for normal tissue homeostasis in particular brain development, and highlight the therapeutic potential of targeting CEP55 in aggressive breast cancer.
Prof Kum Kum Khanna heads the Signal Transduction Laboratory at the QIMR Berghofer Institute of Medical Research. She is best known for her work in the area of cancer biology with a specific focus on understanding cellular responses to DNA damage (DDR) and its links to genomic instability syndromes. Several genes involved in the maintenance of genomic stability when functionally compromised can contribute to cancer formation. Paradoxically, many conventional cancer treatments exploit inherent faults in the regulation of genomic stability present in tumour cells for therapeutic gain. The underlying theme of our research program is to understand the role of genome maintenance pathways in normal tissue homeostasis and in disease – in particular breast cancer. In addition, we are investigating how to exploit dysregulation of these pathways in breast cancer to develop new targeted therapeutic approaches.