2022 PhD Top Up Scholarships

Breast cancer is the most common cancer in Australia, with approximately 20,000 diagnoses and 3,000 deaths in 2020 alone. Most breast cancer patients are diagnosed early enough to be successfully treated with surgery, radiotherapy, hormone therapy and/or chemotherapy. However, 20-30% of patients initially diagnosed with early-stage breast cancer will eventually develop a metastatic disease (when the cancer spreads to other parts of the body). In these cases, chemotherapy is the only treatment option, as these drug types can travel through the body and kill the cancer cells that have spread beyond the original location.
Due to the high rates of relapse and drug resistance seen in chemotherapy, targeted cancer immunotherapies have been developed as alternative treatment options. These therapies boost a patient's immune system, to help the immune cells find and kill cancer cells. However, though these treatments have worked well in some hard-to-treat cancers (e.g. melanoma), their use in breast cancer has not been as successful. One major reason for this is that breast cancer itself is able to "turn-off" important genes which help the immune system to "see" the cancer. In doing so, the cancer cells can stay hidden and survive.
This project aims to use state-of-the-art gene editing technology to design and test a new target treatment that can reverse this process and "turn-on" the important genes that breast cancer has previously "turned-off". If successful, the treatment designed as part of this project will help to make breast cancers more visible to the immune system. Therefore, the patient's immune system will better be able to "see" the cancer and work in combination with other currently available therapies to improve their rates of success. Furthermore, given other cancer types also "turn-off" the same genes, this treatment is likely to benefit other cancers as well (e.g. pancreatic cancer).

Immunotherapies work by boosting the immune system to clear tumours. While there have been impressive results, unfortunately a number of patients fail to respond. This project aims to understand the immune response driving elimination versus cancer escape, which is classically a binary response. Patients either have a ‘hot' immune active tumour which is responsive to therapies or a ‘cold' immune inactive tumour which is unresponsive to therapy. Our early data suggests for successful treatment patients require a balance of both ‘hot' and ‘cold' signals to drive a finely tuned ‘warm' environment. An ‘overheated' response drives a short but ultimately ineffectual immune response, which may explain why some patients with a ‘hot' tumour fail to respond to therapy. Using current technology, we can investigate the mechanisms driving ‘warm' responses to recapitulate them in the laboratory. Using this knowledge, we can stratify patients and deliver personalized therapies to switch them from ‘overheated' or ‘cold' tumours to ‘warm' tumours to improve their response to current therapies.

Mesothelioma is an incurable cancer caused by asbestos exposure. Australia has one of the highest rates of deaths from mesothelioma, with Western Australia having the highest incidence in Australia due to the mining of asbestos in Wittenoom. Chemotherapy is only palliative, with a short survival of 12 months after diagnosis.
Immunotherapy is an exciting treatment for mesothelioma, working to boost a patient's immune cells (in particular T cells) to clear tumours. Clinical trials combining chemotherapy and immunotherapy display complete cures in some cancer patients, whilst other patients gain no benefit. This may be due to each patient having different T cell receptors or keys that need to unlock the immune system to produce a successful anti-tumour immune response.
With the current technology to study millions of keys at the same time, this project will map distinct combinations of keys associated with a successful anti-tumour immune response, to see if we can predict chemo-immunotherapy outcomes.