2025/05/01 by Katie Pickup · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Hepatocellular Carcinoma Treatment and Prognosis #Radiopharmaceutical Chemistry and Applications #Spectroscopy Techniques in Biomedical and Chemical Research
paper · doi:10.1242/dmm.052485
openalex publication_date 2025/05/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/05/06
Liver cancers are a significant cause of death worldwide and incidence continues to rise. Outcomes are often poor, and many current therapies only offer minimal benefits. Improved radiotherapy techniques, such as stereotactic ablative radiotherapy (SABR), have enabled more-precise tumour targeting with reduced damage to the surrounding normal tissue. SABR has been approved for treating hepatocellular carcinoma (HCC), the most common type of primary liver cancer and, while it leads to fewer adverse effects than other therapies, but it does not always prevent tumour growth or recurrence. Better understanding of the impact of SABR in HCC would enable the design of combination therapies and more-effective cancer treatments.Here, May, Bird and colleagues set out to establish a mouse model of HCC, where tumours can be clearly distinguished from the surrounding tissue to enable image-guided treatment with SABR. The authors injected a well-characterised mouse HCC cell line into mouse livers to generate single tumours at the site of injection. They administered an intravenous, liver-specific contrast agent to allow them to discern tumours from the surrounding issue using X-ray based computed tomography (CT) imaging. This method enabled tumour tracking for up to 18 days. Prior to targeting the tumours with SABR, the authors first validated the radiation dose in healthy mice. The selected clinically relevant dose caused DNA damage in the liver-target site–which recovered after two weeks–and these mice showed no health issues six months later. Finally, they used this dose to treat the HCC model mice with SABR, guided by the contrast CT imaging to directly target tumours over the surrounding tissue. This resulted in reduced proliferation of and increased fibrosis in the tumours without causing equivalent damage to the surrounding non-cancerous tissues.This modelling platform provides a novel preclinical setting in which to better understand the molecular and physiological effects of SABR in HCC in both the targeted tumour and surrounding tissue. There is strong clinical incentive to determine whether other treatment, such as immunotherapy, could be effective in combination with SABR to prevent tumour growth and recurrence. Modification of this system will enable research of further treatment options to improve patient outcomes.