Understanding how colorectal cancer resists treatment by studying netrin-1

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The goals of this project are to:

1. Identify which metastatic tumour cells drive the regrowth of colorectal cancer after treatment
2. Characterise the mechanisms underlying the ability of metastatic tumour cells to drive regrowth.
3. Examine and describe the role of the protein netrin-1 and its receptor UNC5B in enabling cancer cells to resist current treatments and to spread to other parts of the body.

The details

Colorectal cancer (CRC) is one of the most common and lethal types of cancer, causing 935,000 deaths worldwide each year. Although treatments are available, patients often relapse after treatment has ceased. The ultimate cause of patient death is metastases forming in vital organs, such as the liver. Metastases are tumours that form in another location away from the primary site of the cancer. They can grow back after treatment stops. Australian patients with metastatic colorectal cancer have a 5-year survival rate of only 13.4 per cent. To date, research has not provided an effective solution to prevent recurrence of CRC after treatment.

Each tumour has cells that are capable of resisting or adapting to drug treatments. A key driver of a cancer’s ability to rebound after treatment is how sensitive the cells within individual metastases (tumours) are to drugs. In some tumour cells, plasticity and the ability to survive increase in response to treatment.

Recent studies suggest that the ability of these cancer cells to resist therapy is linked to a biological process known as the epithelial-to-mesenchymal transition (EMT). Research also shows that the protein netrin-1 and its receptor UNC5B can regulate EMT. By examining the role of netrin-1 and its receptors, this project hopes to make a contribution towards solving the problem of cancer recurrence

Graduate researcher profile: Morgan Brisset

Morgan Brisset:

What did you do before you started your PhD?

Before my joint PhD started in 2020, I obtained a bachelors degree in biochemistry and a masters degree in cancer biology from the University of Montpellier, France. I was initially on the path to becoming a doctor but decided to pursue further research in biochemistry after realising that was where my passion lay.

I completed two internships throughout my masters degree: one at the Functional Genomics Institute of Montpellier, where I worked on colorectal cancer stem cells, and another at the Cancer Research Institute of Montpellier, where I worked on the impact of apoptotic proteins on liposarcoma metabolism.

What are the challenges of your research role? Completing a joint PhD has challenges.

For example, regularly liaising with a supervisor in another country can be difficult. Due to the differences in time zones, you may need to operate on a flexible schedule, which can be difficult when juggling research commitments. The most challenging aspect of my role is dealing with the reality that I won’t always make progress with my research. Progress can be nonlinear, and I often hit roadblocks with my research, which can be pretty demoralising. However, the satisfaction I get when I finally make a breakthrough far outweighs this negative.

What is the best part of your research role?

The best part of my research role is receiving the opportunity to explore the frontiers of knowledge. The ‘Eureka!’ moment when you finally make a breakthrough is a rewarding experience. The responsibility, freedom and ability to discover new things that come with undertaking a PhD are immensely gratifying. Researching at two different institutions exposes me to two different ways of thinking and two different ways of doing things. I found that this adds credibility to my research and also enriches my PhD experience overall. Outside of work, I’ve been able to do some travelling to Sydney and the Great Ocean Road, which has been very enjoyable.

Where do you wish to go after your PhD? Do you want to enter industry or continue doing more research?

After completing my PhD, I wish to pursue a career in academia. I want to become a maître de conférences (MCF) in France, with the ultimate goal of attaining a professorial role. I’ve always enjoyed teaching, and it would be an honour to foster the next generation of scientific talent

Supervision team

• The University of Melbourne: Professor Frederic Hollande
• CNRS: Dr Patrick Mehlen