How the tiny zebrafish might unlock new cancer treatments

Meet the Deakin Research Fellow using cutting-edge genome-editing techniques to create zebrafish models of human cancer.

Dr Faiza Basheer is interested in deciphering the drivers of aggressiveness and drug resistance in solid cancers, particularly colorectal cancer and melanoma. Since completing her PhD with Deakin in 2018, Dr Basheer has gone from strength to strength.  

To carry out this unique research Dr Basheer and her team use the zebrafish. The small fish may seem out of place in a laboratory, however, it has proved to be a useful model for scientists to study human cancers. Dr Basheer aims to use a novel optically-clear immune-deficient zebrafish model that was recently developed at Deakin University to determine the mechanisms underlying the growth and spread of colorectal cancers. 

Dr Basheer and her colleagues at the Gene Regulation and Oncogenesis laboratory at Deakin’s School of Medicine is one of the few labs in Australia carrying out this unique line of research. 

Dr Basheer in the Gene Regulation and Oncogenesis laboratory
Dr Basheer in the Gene Regulation and Oncogenesis laboratory

Treating one of Australia’s deadliest cancers

Dr Basheer and her team are currently studying colorectal cancer and how it spreads to other parts of the body in a process known as metastasis.  

Colorectal cancer, also known as bowel cancer, was the 2nd deadliest cancer in Australia in 2019, only behind Lung Cancer. Every year, 15,000 Australians are diagnosed with this aggressive form of cancer, and it claims the lives of 5,000 Australians annually.  

Dr Basheer says ‘the majority of the colorectal cancer patients die not due to their primary tumour, but mainly because of the challenge associated with managing multiple secondary tumours. Therefore, to help this situation, it is necessary to understand the factors that make these cancers highly aggressive. 

‘The major concern associated with treating these patients is that currently, we do not have effective ways to block or prevent the tumour spread and it’s a great challenge to treat once the tumours are spread.’ she says. 

To spread throughout the body, the cancer cells must leave the primary site and overcome several barriers to be able to successfully colonise other parts of the body.  

‘However, we know that for metastasis to occur these cancer cells must overcome the human immune system. In most cases, these cancer cells will be recognised by the immune cells which will eventually kill them. 

‘However, a small proportion of them escape the immune system to reach these secondary sites and create tumours in the body. These secondary tumours can develop within months or even many years post anti-cancer treatment. Recent studies have identified that a protein called FRA1 is critical for the aggressive nature of colorectal cancer.’ says Dr Basheer.  

Identifying new strategies to battle this process is the core of what Dr Basheer is trying to achieve. If her research is effective, it could lead to novel treatments to help patients with advanced colorectal cancers that presently cannot be treated. 

Dr Basheer and colleagues in the Gene Regulation and Oncogenesis laboratory
Dr Basheer and colleagues in the Gene Regulation and Oncogenesis laboratory

So, where does the tiny zebrafish come into play?

Humans are much more like zebrafish than you might think. In fact, 84% of the genes found in the human genome are the same as those found in zebrafish.  

The spread of cancer can only be studied in vivo, most commonly by xenotransplanting human cancer cells into mice. However, these models are time-consuming, expensive and require sophisticated imaging equipment. This is where the novel immune-deficient zebrafish model becomes powerful and beneficial. Unlike mouse models, zebrafish xenotransplantation can be performed much faster, on a larger scale, and allow non-invasive imaging of the fate of individual cancer cells. 

This zebrafish model is expected to provide important insight into the key problems in our current understanding of cancer biology, specifically in understanding the mediators of tumour spread. The research that Dr Basheer’s team are conducting is the first of its kind in Australia. 

‘What is different about the zebrafish is that it allows us to actually look at human cancer cells in real-time in a non-invasive way. This is highly effective to explore ways we can target therapies and treatments for a range of other aggressive cancers.’ 

– Dr Faiza Basheer

Zebrafish transplanted with human colorectal cancer cells 1 day and 14 days post-injection 
Zebrafish transplanted with human colorectal cancer cells 1 day and 14 days post-injection

Dr Basheer has mastered the xenotranplantation technique that enables her to transplant cancer cells into the immune-deficient zebrafish without any immune rejection. The team use fluorescent dyes to track the cancer cells that are transplanted into the immune-deficient zebrafish and utilises a fluorescent microscope to track the later stages of metastasis.  

‘Thus far, the team used this model in conjunction with gene knockdown technology to validate the role of a protein called FRA1 in driving colorectal cancer metastasis. 

‘Zebrafish allow us to study the therapeutic effects of potential drug targets much quicker and at a larger scale than mice, which is immensely useful to fast-track the development of these important therapies. This is why the zebrafish is such a powerful little tool to conduct such studies.’ says Dr Basheer. 

However, Cancer research isn’t an overnight success. There is still a significant amount of work that needs to be done before therapeutics can be created. Next, Dr Basheer hopes to use real patient-derived samples to test how well these therapeutics work to block colorectal cancer metastasis. 

Interested? Find out more about the Infection, Immunity and Cancer theme at IMPACT here.