My research focus was to understand how cancer cells learn how to survive in the body. Inappropriate survival can be intrinsically linked to every stage of tumour progression, from the initiating event and growth, its invasion through surrounding tissues, dissemination to distant organs and to the acquisition of therapeutic resistance. An understanding of these processes allows us to discover new therapeutic strategies capable of re-educating cancer cells to die. Although my model systems have been predominantly in breast cancer, I have translated these discoveries to cancers arising in other organs; particularly those with poorer survival outcomes, such as pancreatic cancer. It has been my ultimate goal to translate my discoveries into new treatments and improved clinical outcomes for patients suffering the most lethal forms of breast and other malignancies.
I am an expert in mammary development (Oakes et al 2008, Genes and Dev; Oakes et al 2008 J of Mammary Gland Biology and Neoplasia; Oakes et al 2017 PloS Genetics), carcinogenesis (Oakes et al 2007 Oncogene; O’Toole et al 2013, J. Clinical Pathology) and cancer cell survival (Oakes et al 2012, PNAS; Young et al 2016, Breast Cancer Research; Young et al 2018 Cell Adhesion and Migration, Alexandrou et al 2019).
I have made two major discoveries that have made significant impacts on health and medicine. The first, as post-doctoral scientist at WEHI, where I showed that the BCL-2 antagonist ABT-737 could be used to sensitize triple negative breast cancer cells to routine chemotherapy (Oakes 2012, PNAS). ABT-737 is the lead compound that eventually led to the development of the Australian TGA approved drug Venetoclax and as a result of this research, Venetoclax is now under investigation in clinical trials in multiple cancers including breast cancer. In trials in estrogen receptor positive breast cancer led by my previous lab head, the clinical benefit rate was 72%.
My second major discovery as senior author defined a new role for the pro-survival protein myeloid cell leukaemia 1 (MCL-1), as a regulator of SRC family kinase signalling during invasion. My laboratory showed that that targeting MCL-1 could increase sensitivity of triple negative breast cancers to SRC family kinase inhibitors (Young 2017 BCR; Young 2017 Cell Adhesion and Migration, PCT/AU2017/05132). This discovery led us to search for other cancers that may rely on MCL-1 for survival. We have now discovered high MCL-1 is a strong predictor of worse outcome for up to 75% of all pancreatic adenocarcinoma patients and that MCL-1 antagonism significantly improved the anti-invasive effects of dasatinib. With an incidence to mortality ratio of 94%, and highly potent and specific inhibitors of MCL-1 now in P1 clinical trials, this research has the potential to have a significant and rapid impact in pancreatic cancer.
Community Engagement/Participation (last 5 years only