Proteomics

PROTEOMICS

Proteins are vital components of living organisms, with many functions. “Proteomics” is the area of science dedicated to the large-scale study of proteins. In our proteomic research, we examine how our proteins change when a person develops cancer, or how certain proteins change as patients are treated with different therapies. Through studying the changes in the proteome, we can identify proteins that could help in identifying if a person is at high-risk of developing cancer (or assist in the diagnosis of cancer), or help tailor their treatment to their molecular profile for improved patient outcomes. In collaboration with the Australian Proteome Analysis Facility (www.proteome.org.au), we use the latest-generation protein mass spectrometry to profile cancer cell lines and patient samples to answer urgent clinical questions in lung, pancreatic and brain cancers.

  1. Investigating patterns of drug resistance in ALK rearranged non-small cell lung cancer

Dr Malinda Itchins, A/Prof Nick Pavlakis, Prof Stephen Clarke; Dr Chee Lee; Dr Sarah Hayes and A/Prof Viive Howell

This is a largely non-smoking related lung cancer, characterised by a change to the ALK gene, often affecting a young and fit population. It behaves very differently to smoking related lung cancers and whilst very treatable with targeted therapy, resistance to such treatment is inevitable. We want to investigate how resistance to these drugs develops in these patients, and if resistance can be avoided through scheduling drug cycles. In the lab, this involves the protein profiling of several ALK lung cancer cell lines which we have made resistant through continual treatment with drugs usually used in the clinic to treat ALK lung cancer to see how this resistance develops.

Funding: NSW Health, donations from the Schnell Family 

  1. Identification of biomarkers for Non-Small Cell Lung Cancer

Dr Sarah Hayes, Dr Csilla Hasovits, Ms Rozelle Harvie, Dr Amanda Hudson, Prof Stephen Clarke, A/Prof Nick Pavlakis, A/Prof Mark Molloy (Australian Proteome Analysis Facility), A/Prof Viive Howell

Lung cancer is the second most common cancer in men and women and a leading cause of cancer-related deaths worldwide.  This large, multi-faceted project aims to tackle several unanswered questions. How do our proteins change when a person develops lung cancer? Can we predict which therapies are best for each individual patient based on their protein profile? What happens when a patient becomes resistant to therapy? We are investigating into all of these areas through profiling lung cancer cell lines and patient samples (like blood, breath and tumour) using cutting-edge mass spectrometry. We are ultimately hoping that this research can be used to assist in the earlier diagnosis of patients, prediction of patient prognosis or to helping guide personalised cancer treatment selection.

Funding: Tour de Cure 2018 Scott Canner Early Career Fellowship and support from Fight for a Cure

  1. The exhaled breath condensate proteome: a promising source of biomarkers for lung cancer

Dr Sarah Hayes, Prof Stephen Clarke, A/Prof Nick Pavlakis, A/Prof Mark Molloy, A/Prof Viive Howell

In recent years, there has been increasing interest in using exhaled breath as a tool for screening, diagnosing, and even monitoring diseases of the airway, including lung cancer. Changes in specific proteins found in exhaled breath of lung cancer patients may be an indication of the underlying cancer, presenting a potential screening technique for early detection of this disease. Sampling a patient’s breath only involves 15 minutes of breathing out into a specialised tube and is safe, non-invasive and simple to collect. In this project, we are using cutting-edge mass spectrometry to comprehensively map proteins found in human breath from lung cancer patients to identify these proteins. This is the first time ever that the human lung cancer breath proteome (which we have termed the “breathome”) has been profiled by mass spectrometry.

Funding: Tour de Cure 2018 Scott Canner Early Career Fellowship and support from Fight for a Cure. Previous funding included Cancer Institute NSW and Balnaves Foundation/Sydney Medical School.

  1. Laying the foundations for improved treatments for IDH-mutated glioma (brain cancer)

Angela Cho, Dr Sarah Hayes, Dr Amanda Hudson, Dr Emily Colvin, A/Prof Michael Back, Prof Stephen Ackland (Hunter Medical Research Institute), A/Prof Helen Wheeler and A/Prof Viive Howell

Low grade gliomas are characterised by a relatively indolent clinical course and a good prognosis. However, these gliomas may recur as high grade gliomas, which are more aggressive and are difficult to treat. Our goal for this research is to better understand the mechanisms which may drive the change in behaviour of these tumours when they recur. To do this, we are comparing the proteomes of original low grade tumour and the aggressive, recurrent brain tumour to identify key proteins that are involved in the recurrence of this disease. Understanding how these tumours change over time and in response to therapy will lay the foundations for developing better treatments for this rare form of brain cancer.

Funding: Mark Hughes Foundation, Hunter Medical Research Institute, Sydney Neuro-Oncology Group and University of Sydney and Balnaves Foundation

5. Exploring methods to improve efficacy of immunotherapy in non-small cell lung cancer (NSCLC)

Dr Malmaruha Arasaratnam, Dr Sarah Hayes, Dr Kelly McKelvey, A/Prof Viive Howell and A/Prof Nick Pavlakis

Our research project is exploring methods to improve effectiveness of immune therapy in lung cancer. We will be using proteomics to identify if there are proteins secreted in blood that can predict which patients respond well to therapy and which do not. In patients that are unlikely to respond, alternative treatment options can be explored.

Funding: Sydney Vital Postgraduate Scholarship in Immunotherapy in Non-Small Cell Lung Cancer