The paper, An α-specific PI3K inhibitor improves chemotherapy efficacy by inhibiting hepatic stellate cell activation in liver cancer, is from an area of research where the team is investigating the environment surrounding the tumour.

Liver Cancer Research Lead and the paper’s corresponding author, Dr Xiaowen (Tina) Liang, compared the approach to research as seeing the tumour as a weed, where the team is examining the tumour’s soil and how it works to support the weed—the tumour. They then studied ways to alter the soil to inhibit tumour growth. and then how that soil be altered to reduce tumour growth.

“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,” said Dr Liang.

“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.

“Using human cancer cells, preclinical models, and tumour sample from patients, we found the pathway by which chemotherapy activates these HSCs. We then used an FDA-approved drug called alpelisib to target an important element of the pathway and this reduced tumour burden by 68 per cent compared to chemotherapy without alpelisib.

“By learning more about these interactions, we will find ways to make the ‘soil’ less supportive for the tumour, helping treatments work better and improving outcomes for patients. Our findings strongly support a trial to repurpose alpelisib in combination with chemotherapy for primary liver cancer. This treatment approach may also be helpful in other types of cancer,” she said.

GMR’s Head of Research Professor Darrell Crawford said publishing in the journal was an incredible achievement for the team.

“The liver team has worked together to have this paper published in Hepatology, which deals with some of the adverse effects of treatments for liver cancer on the underlying liver damage,” Professor Darrell Crawford said.

“Publishing in this journal means we can share our findings with the international liver research community, and we all take one step closer towards a better understanding of liver cancer and how we can reduce its burden on patients.”

Hepatology is the flagship journal of the American Association for the Study of the Liver.