GU cancer

Exosomes may be key to changing the conversation in ovarian cancer

Tuesday, 26 May 2020

Can you sum up this research project in 10 words?

This project utilises exosomes for real-time monitoring of ovarian cancer progression.

What have you previously discovered in this area?

When ovarian cancer is identified early, treatment reduces the possibility of progression to an aggressive phenotype by 80%. Recently, we completed a project analysing the protein and miRNA changes within exosomes obtained from women at different stages of epithelial ovarian cancer and benign disease. Based on the data obtained, we developed a multimarker classification that delivers positive and negative predictive values >90%. In addition, we have identified a set of molecules (e.g. proteins and miRNAs) within exosomes that increase in association with the progression of disease, chemotherapy resistance and cancer recurrence. Thus, we propose that exosomes transfer oncogenic activity to cells within the tumour microenvironment to facilitate cellular invasion. Currently, we are evaluating the use of exosomal biomarkers for earlier and accurate identification of women at risk of developing chemotherapy resistance, thus allowing earlier implementation of personalised treatments using a novel biomimetic delivery system.

What’s fascinating about extracellular vesicles?

Tumour development and progression is dependent upon cell-to-cell communication, allowing cancer cells to not only re-program cells within the surrounding tumour microenvironment, but also cells located at distant sites. Recent studies established that extracellular vesicles (EVs), particularly exosomes, mediate bi-directional communication between normal and cancerous cells. EVs are packaged with tissue-specific signalling molecules (e.g., tumour markers) and once released, are capable of regulating target cell phenotype, inducing a pro-tumorigenic phenotype to contribute to tumour growth and metastasis as well as proximal and distal cell function. EVs have many advantages over traditional “soluble” biomarkers that are present in biofluids, such as their stability in vivo and in storage, and their utility as a non-invasive biopsy. We have proposed that EVs provide a “fingerprint” of their cell of origin and reflect the cellular metabolic status.

What aspect of this ovarian cancer research excites you the most?

Our biggest challenge with ovarian cancer is the lack of tools to detect the disease at an early, treatable stage. While some progress has been made, there has been little improvement in survival rates over the last 20 years. Early stage ovarian cancer is not associated with overt symptoms and there is a lack of reliable diagnostics. I think the opportunity to develop an early diagnostic test is exciting, because if the cancer is identified at an early stage (i.e. stage I and II), the 5-year survival rate is over 90%.

What is your biggest research hurdle?

From the scientific point of view, the major contributing factors to the high mortality rates are the lack of clinically useful biomarkers for earlier detection of ovarian cancer and for assessing responsiveness to chemotherapy; and unfavourable bio-distribution and low penetration of therapeutic agents into tumour cells. This project will directly address these factors, highlighting the significance and impact of our proposal.

How long before this work might impact on patient care?

We hope that our panel will be validated within the next 5 years, and if the performance of the test is maintained or even improved at the end of the grant timeline, we will have the opportunity to implement the panel as an early detection test in clinical practice. Our study will be conducted in compliance with Good Laboratory Practice (GLP) and Good Clinical Practice (GCP) principles as informed by ISO17025, at UQ Centre for Clinical Diagnostics, a facility accredited by the National Association of Testing Authorities (NATA), thus, enhancing the likelihood of translation of our discoveries into clinical practice.

What’s your Holy Grail – the one thing you’d like to achieve in your research career?

My career goal is to pursue my interest in human health and make a real impact on the quality of life of Australians by facilitating translation of academic research discoveries into clinical applications, and became a leader in this field. At some point I want to translate discovery into clinical practice and help our community, as well as achieve a global impact. That is why we are doing this.

Who has inspired you most – in work or life?

I grew up with my great grandmother, who passed away a couple of years ago at the age of 100! I saw her working from very early in the morning until late at night for many years, and every time that I feel tired or disheartened, I think about her. I am a family man, and my wife and kids inspire me every day.

How do you maintain work-life balance?

I have a passion for sports and hence spend time playing basketball as well as doing outdoor activities with my wife and children (4 year old son and 2 year old daughter). I am a member of a local basketball club in Brisbane, and I play at the Basketball Brisbane League once per week. I have also been a member of the Lions club for the past 3 years and participate in their activities, including programs for our youth, medical research and health related activities, assistance to adults and children with disabilities and response to emergencies or disasters.

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