Finding new ways to overcome advanced bowel cancer drug resistance

Australia has one of the highest rates of bowel cancer in the world, with over 15,000 Australians estimated to have been diagnosed this year.  

On top that, bowel cancer is Australia’s second biggest cancer killer – more deadly than breast, prostate, or skin cancer. 

While early detection improves treatment outcomes, advanced cases often see challenges due to drug resistance.  

That’s where Professor Xu Dong Zhang’s project comes in, which looked at identifying new treatment options for people with advanced bowel cancer. 

Understanding the ERAG molecule’s role in bowel cancer 

Prior to getting funded in 2021, Professor Zhang and his team found a molecule called ‘endoplasmic reticulum stress and apoptosis related genes’ (ERAG) – often present in high levels in bowel cancer cells. 

By simply removing ERAG, the cancer cells became more sensitive to treatment and stopped growing, revealing a potential new way to treat bowel cancer. 

To test this, the team were using tumour samples from patients to test their previous findings in pre-clinical tests and measure levels of ERAG in patients, to predict their response to treatment.  

The team then went on to develop and test new drugs known as ‘IoEs’ which target and prevent the activation of ERAG. 

Key milestones and discoveries 

Since the project started, the team set themselves four goals to set a path towards identifying new treatment options for people diagnosed with advanced bowel cancer. 

1. Learn the protective role of ERAG. 

Using cancer cell lines, the team confirmed the central role of ERAG in protecting cancer cells from oxidative stress.  

ERAG achieves this through the pentose phosphate (PPP) pathway – a cellular signalling path used for cell survival.  

The team also discovered how ERAG regulates the activity of the PPP pathway. 

2. Look into how ERAG affects G6PD and the pathway it’s involved in. 

Using cellular and molecular biology techniques, the team learned how ERAG interacts with a molecule called G6PD – an important component of the PPP pathway – and how this interaction promotes PPP pathway activity.  

3. See if ERAG has any links to cancer development and how it affects cancer outcomes. 

The project team explored whether ERAG is associated with colorectal cancer development and cancer outcomes.  

Despite limited access to clinical samples due to the COVID-19 pandemic, the team were able to accelerate their experiments throughout 2022 and 2023 to achieve this goal. 

4. Explore therapeutic potential of ERAG inhibition. 

As expected, the combination of ERAG inhibition and existing drugs improves the treatment response of bowel cancer in models.  

These findings show a promising future for innovative therapies targeting ERAG. 

Future of bowel cancer treatment options 

Professor Zhang and his team will work with pharmaceutical companies specialising in drug development to create new drugs that will treat bowel cancer by inhibiting ERAGs.  

From there, the team intend to develop an easy-to-use, low-cost lab kit for testing ERAG expression, benefiting low-income families and rural communities. 

With pre-clinical and early clinical trials on the horizon, the team remains committed to advancing cancer care. 

As cancer research continues move forward, we need your support to help fund more research. 

Because it’s all of us against cancer. 

Professor Zhang’s research has been funded by a Cancer Council project grant awarded in 2021.    

To support more life-saving cancer research and programs, consider making a donation today.