ONJCRI researchers have made a crucial discovery about the way in which colon cancers progress. This exciting study has the potential to change the way we treat these tumours in the future.


15,200 Australians were diagnosed with colon cancer in 2021. It is the third most common cancer in Australia and is the second deadliest cancer for Australians.

A new study led by ONJCRI researchers has made a breakthrough discovery that may change the way we treat colon cancer tumours in the future.

Dr Ian Luk, a Postdoctoral Research Fellow in the ONJCRI’s Oncogenic Transcription Laboratory, explains that understanding how tumours develop and progress is fundamental to finding better therapies and treatments for patients.

“Looking under a microscope, the structure of the colon tissue is very distinctive displaying very organised glandular structures. However, in colon cancer, some tumours lose these structures in a process called loss of differentiation, meaning that the tumour has lost its sense of identity.”

Dr Luk explains that tumours that lose differentiation tend to be more aggressive and more resistant to conventional chemotherapy, meaning patients generally have worse outcomes.

“These tumours also have a much higher chance of metastasising to other areas of the body, so understanding what causes these tumours to lose differentiation is really important.”

In this study, the team were able to identify two genes, EHF and CDX1, that are inactivated in poorly differentiated tumours. Using a mouse model of colon cancer, the team found that when these two genes were deleted, tumours had lost differentiation and there was an increase in tumour number and size. Using a separate model, they also found that re-introducing EHF and CDX1 into colon cancer cell lines had reduced metastasis when injected into mice.

“This study was significant because it clearly demonstrates that when these two genes are co-ordinately inactivated in colon cancer, it drove the loss of differentiation as well as increased tumour progression, meaning that the cancer can grow and spread more rapidly. Interestingly though, when we remove these genes individually, the same effects were not observed It was only when they were removed together that we observed these exciting findings.”

Upon uncovering this breakthrough, the team plans to find therapeutic avenues to ‘reactivate’ the genes.

“The exciting thing about this, is that now we know that by reactivating these genes in colon tumours we can potentially slow the growth, prevent metastasis and even potentially sensitize these tumours to conventional therapies,” said Dr Luk.

The ONJCRI team is excited about where this study could lead.

“This is a first but important step in an interesting and understudied area of research. To develop new therapies and treatments that target this subgroup of colon cancers, we first need to understand what makes them different from other tumours that respond to traditional treatments.”

“One of the great things about cancer research is the collaborative environment. We hope that together with other researchers we can now utilise this knowledge to develop therapeutic avenues based on reactivating these genes in colon cancer so that patients can have better outcomes.”