Sorafenib is a first-line therapy used to treat advanced liver cancer, but its effectiveness is often reduced due to resistance in cancer cells. This study co-led by N2CR member, A/Prof Gautam Sethi, explored the biological mechanisms behind that resistance and identified a group of genes involved in retinoic acid metabolism that help cancer cells survive treatment.

These genes are activated by a protein called POU3F3, which boosts the production of retinoic acid—a compound that protects cells from damage. By silencing POU3F3, researchers were able to make cancer cells more responsive to sorafenib. They also identified a compound called rosarin that inhibits POU3F3 and enhances the drug’s effectiveness. Laboratory and animal tests showed that combining rosarin with sorafenib significantly improved treatment outcomes. These findings suggest that targeting POU3F3 could be a promising strategy to overcome drug resistance and improve the success of liver cancer therapies.

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