Fueling chemotherapy resistance in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a molecularly heterogeneous group of diseases defined by the lack of estrogen receptor (ER), progesterone receptor (PR) and absence of human epidermal growth factor receptor-2 (HER2) amplification. Consequently, TNBCs are impervious to therapies commonly used in other breast cancer subtypes and treatment options are largely limited to conventional chemotherapy agents. Approximately 30% of TNBC patients respond to chemotherapy. Unfortunately, the long-term prognosis for the majority of patients with residual disease after chemotherapy is poor.

Identification of novel and actionable strategies to sensitize cancer cells to chemotherapy would represent a major advance for the management of TNBC. Cancer cells exhibit dramatic alterations in cell metabolism, which support cell growth, proliferation and survival. Indeed, metabolic reprogramming is a recognized hallmark of cancer induced by numerous genetic or epigenetic alterations. Our recent studies suggest that reprogramming of cellular metabolism is also a component of the highly coordinated response to chemotherapy exposure. The aims of this project will be to:
1) identify adaptive metabolic reprograming events triggered upon chemotherapy exposure, and
2) identify novel therapeutic approaches to exploit adaptive metabolic reprogramming events and sensitize TNBC cells to chemotherapy.

This research will lead to the identification of critical mechanisms driving chemotherapy resistance in TNBC and establish combination therapy strategies with potential to have a major impact on patient survival. Students will gain experience in mammalian cell culture, molecular biology techniques, metabolomics and stable-isotope labelling techniques.

The Brown laboratory investigates mechanisms that drive resistance to chemotherapy and targeted therapy agents in breast cancer.
This knowledge is applied to the pre-clinical development of novel and more effective interventions for breast cancer therapy.
https://www.petermac.org/research/labs/kristin-brown

Peter MacCallum Cancer Centre in Melbourne Australia’s only public hospital solely dedicated to cancer, and home to the largest cancer research group in Australia. Cancer is a complex set of diseases, and modern cancer research institutes such as Peter Mac conduct research covering a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell growth, translational studies that seek more accurate cancer diagnosis, clinical trials with novel treatments, and research aimed to improve supportive care.
https://www.petermac.org/education/research-education

All students engaged in postgraduate studies at Peter Mac are enrolled in the Comprehensive Cancer PhD (CCPhD) program, regardless of which university they are enrolled through. The program is managed by the Sir Peter MacCallum Department of Oncology (The University of Melbourne), based at Peter Mac.

The Comprehensive Cancer PhD program builds on established conventional training for cancer research students providing a coordinated program of skills, research and career training in addition to usual PhD activities. The program is designed to complement existing PhD activities and provides opportunities to develop professional skills that will help candidates to fulfil their career ambitions.
https://www.petermac.org/education/comprehensive-cancer-phd-program