Research

Our laboratory investigates the bi-directional interaction between the brain (or nervous system) and the tumour microenvironment.

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Neural regulation of metastasis View

Top: LYVE-1 staining of lymphatic vessels in a tumour. Bottom: Tumour cells invading through extracellular matrix.

Metastasis, or cancer spread, is the leading cause of morbidity and mortality of cancer, but little is known about physiological factors that regulate this process. Our studies have shown that chronic stress acts through the SNS to accelerate metastasis of breast and pancreatic cancer.

We have shown that when stress is transmitted through the body via beta-adrenergic signalling pathways it helps tumour cells to move out of the primary tumour and spread to distant sites. We have shown that chronic stress signaling recruits immune cells to the primary tumour. In their intended role, these cells help our immune system fight off disease. However, cancer hijacks the immune system to assist tumour cells disperse throughout the body to colonise vital organs.

Results of these studies are guiding a clinical study of beta-blockers in cancer patients and are aiding the development of novel therapeutic strategies that target this beta-adrenergic regulation of metastasis.

Cancer treatment and cognitive impairment View

Trace from locomotor activity test used to assess anxiety-like behaviour in mice.

Chemotherapy has revolutionised treatment of cancer patients, but it often results in long-term neurological and cognitive side-effects (known as 'chemobrain'). While chemotherapy kills the cancer, patients can suffer from learning and memory problems, fatigue and depression that can remain long after treatment has stopped. The severity of chemobrain can significantly impact the quality of life of cancer survivors or even lead to changes in a patient's treatment plan. Little is known about what causes these adverse effects of cancer treatment.

Dr Adam Walker leads a research program in association with our lab that investigates how cancer, surgery and chemotherapy induce negative effects on the brain. Using preclinical models of cancer and ageing brains, his results so far are demonstrating how cheap and readily available drugs such as aspirin could prevent these debilitating side-effects of chemotherapy and improve the quality of life of cancer survivors.

Targeting perioperative stress to improve cancer outcomes View

Surgery is critical to the management of cancer. However, factors associated with surgery including physiological stress and immunosuppression may amplify the risk of cancer recurrence. This identifies the perioperative period as a unique therapeutic window for additional intervention.

Importantly, the choice of medications that patients receive during surgery may provide a way intervene in surgical stress and improve long term outcomes. While anaesthetic techniques have the common goal of blocking pain and sensation, some anaesthetic agents may protect against inflammation and surgical stress.

Our lab is investigating the impact of anaesthetic agents and adjuncts on long-term cancer outcomes including recurrence and metastasis. These studies will be valuable to inform the design of large, prospective, multi-centre clinical studies looking into the use of anaesthetic agents to improve cancer outcome.

Collaborations

Prof Bernhard Riedel, Peter MacCallum Cancer Centre
A/Prof Scott Mueller, University of Melbourne
Dr Stephen Mattarollo, University of Queensland
A/Prof Amy Rowat, University of California Los Angeles
Prof Steve Cole, University of California Los Angeles
Dr Edoardo Botteri, Norwegian Cancer Registry
Prof Stephen Hill, University of Nottingham

Funding

National Health and Medical Research Council
Australian Research Council
US National Cancer Institute and NCI Network on Biobehavioral Pathways in Cancer
Skewes Foundation
Peter MacCallum Cancer Foundation
National Breast Cancer Foundation

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Monash Institute of Pharmaceutical Sciences