Targetting genes with the potential to cause breast cancer

Dr Andrew Burgess, an experienced cell biologist who is the Institute’s new Microscopy and Cytometry Manager, has been awarded a grant of $398,049 over three years by the National Breast Cancer Foundation to further his research into the genetic background of breast cancers.

A primary driving force behind the initiation and ongoing development of breast cancer is the activation of oncogenes, genes with the potential to cause cancer. Dr Burgess explains that oncogenes act like a car accelerator, driving excessive growth and spreading of the cancer cells throughout the body. Consequently, identifying new oncogenes and determining their functions is essential for understanding how breast cancers grow and spread.

“We recently identified a novel oncogene called MASTL that is amplified and overexpressing up to 45% triple-negative breast cancers (TNBC). Importantly, increased MASTL correlates with higher grade, unstable tumours and poor patient survival. Our preliminary data shows that MASTL is able to drive normal breast cells to grow and spread abnormally.

“Conversely, removal of MASTL from TNBC cells reverses the abnormal growth and spreading. Initial analysis of the underlying mechanisms suggests that MASTL rewires key signalling pathways in breast cells and is essential for regulating how cells duplicate their DNA. We hypothesise that MASTL is an ideal candidate to develop inhibitors, as blocking MASTL would prevent breast cancer growth and spreading, and enhance response to current chemotherapies, leading to improved patient survival.

“The purpose of this project is to better understand the mechanisms by which MASTL drives breast cancer, confirm that targeting MASTL can successfully block breast cancer in mice models, and to establish the tools necessary to develop specific inhibitors of MASTL that could be used to treat breast cancer.”

Dr Burgess expects this project will primarily benefit patients with TNBC, especially metastatic disease. These patients are normally unable to undergo curative surgery, are unresponsive to hormone therapy, and therefore chemotherapy is the only treatment option. Unfortunately, the majority (~80%) of patient tumours do not respond to current chemotherapy treatments, and very few new treatments have been developed. Consequently, metastatic TNBC has some of the lowest overall survival rates for breast cancer and these have not improved in the past 20 years.

“There is a significant need to identify new targets for TNBC in order to improve these worst-case patients. We believe that MASTL represents a promising new target that could be used to improve the outcomes for TNBC patients.”

In 2017 it was estimated that almost 18,000 Australians (including about 150 men) would have been diagnosed with breast cancer, and at least 3000 deaths would be recorded.

Dr Burgess joined the ANZAC Research Institute in 2017, after five years at the Kinghorn Cancer Centre within the Garvan Institute of Medical Research. His career began in 1998 as an honours student at the Queensland Institute if Medical Research, and after graduating with 1st class honours, he studied for a PhD at the University of Queensland. In 2004 he was awarded a prestigious NHMRC C J Martin fellowship, which took him to the French National Research Centre in Montpellier. Two additional French fellowships allowed him to remain in France for seven years, continuing to explore the basic mechanism of how cells control the division process. In 2012 Dr Burgess received a five-year Fellowship from the Cancer Institute NSW which led to his return to Sydney.