Dr Xiaowen (Tina) Liang
Liver Cancer Research Lead,  Gallipoli Medical Research
Research Fellow, University of Queensland

A diagnosis of liver cancer often arrives quietly, but its impact is devastating. For many patients and their families, it brings uncertainty, limited treatment options, and survival odds that remain stubbornly low.

In 2020, liver cancer was the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. In Australia, the incidence of liver cancer has tripled during the last 30 years due to increasing alcohol consumption and non-alcoholic fatty liver disease (itself often caused by obesity, diabetes, high blood pressure and high cholesterol).

Veterans—men and women who have already carried the burden of service—face an even higher risk. Data from the United States suggests liver cancer is five times more common among veterans than the general population, compounding the long-term health consequences many already endure post-service.

Behind our work in liver cancer research is the simple, but urgent, question: how can we give patients a better chance at survival?

Chemotherapy treatments such as transarterial chemoembolisation (TACE) and systemic chemotherapy are commonly used for primary liver cancer. However, these treatments often have low response rate, and the overall five year survival rate for liver cancer in Australia is still low: about 24–25% of people living at least five years after diagnosis.

One major reason many patients do not respond well to current treatments is because non-cancer stromal cells in the tumour microenvironment actually help protect tumour cells from therapy. In primary liver cancer, activated hepatic stellate cells (HSCs) are the main origin of stromal cells. They form a supportive ‘soil’ that nurtures the tumour ‘seed’, promoting its survival, growth, and resistance to treatment.

Even when chemotherapy attacks the tumour ‘seed’, the surrounding ‘soil’ can quietly protect it — shielding cancer cells and helping them grow back stronger. For patients, this means enduring difficult treatments without the reassurance that they will work.

Accordingly, An α-specific PI3K inhibitor improves chemotherapy efficacy by inhibiting hepatic stellate cell activation in liver cancer study aims to understand how standard treatments like TACE and chemotherapy affect the non-cancer stromal ‘soil’ and what biological processes drive these changes. By learning more about these interactions, we hope to find ways to make the ‘soil’ less supportive for the tumour, helping treatments work better and improving outcomes for patients.

Gallipoli Medical Research PhD student, Dr Qi Ruan, conducted extensive experiments for this project using both laboratory (in vitro) and animal models of liver cancer during her PhD, under the supervision of me and GMR Director of Research, Professor Darrell Crawford. Our study shows platinum based chemotherapy drugs can trigger activation and accumulation of HSCs in the tumour microenvironment, which helps the tumour resist therapy and makes the treatment act like a double-edged sword. This activation happens mainly through a signalling pathway called PI3K, and we also confirmed these findings by examining tumour tissue samples from patients with primary liver cancer.

Based on these findings, we repurposed an existing FDA approved drug (alpelisib), a PI3K inhibitor originally used to treat breast cancer with PIK3CA mutation, to block a PI3K pathway and prevent the activation of HSCs and tested how well it works in combination with chemotherapy in preclinical liver cancer models.

The results were striking. When combined with chemotherapy, alpelisib reduced tumour burden by 68% compared with chemotherapy alone — a finding that suggests we may finally be able to weaken the tumour’s defences while attacking it more efficiently. For patients facing limited options, this represents more than a laboratory result—it represents hope.

Our study provides an effective approach to treat liver cancer, offering a new strategy that not only destroys the tumour ‘seed’ but also disrupts the supportive ‘soil’. These promising results give us strong confidence to move forward and explore this combination in future clinical trials with the goal of helping more patients with liver cancer and potentially expanding to treat other types of cancer.

While this work has been recognised internationally through major awards and publication in Hepatology, its true significance lies elsewhere—in the possibility of extending lives, easing suffering, and offering renewed hope to patients and families confronting liver cancer.