Scientists Discover Protein That Enables Liver Cancer to Survive Heat Treatment

A recent study led by researchers at UCLA Health's Jonsson Comprehensive Cancer Center sheds light on why some liver tumors recur quickly after thermal ablation, a common minimally-invasive procedure that destroys cancer cells by applying intense heat via a needle-like device. The researchers identified the sugar-binding protein Galectin-1 (Gal-1) as a key factor that helps primary liver cancer, or hepatocellular carcinoma, resist this heat-based therapy and even thrive afterward.

The study found that Gal-1 plays a critical role in cancer cell survival by enhancing their energy production through sugar metabolism, which allows them to withstand thermal stress. Dr. Jason Chiang, senior author and assistant professor of Radiological Sciences at UCLA, explained that Gal-1 boosts the metabolic pathways in cancer cells, especially glycolysis and the tricarboxylic acid (TCA) cycle, providing the necessary energy for these cells to recover and proliferate quickly following ablation.

This metabolic resilience contributes to the high recurrence rate observed in up to 40% of patients after thermal ablation, often at the tumor margins where heat may not be sufficient. The researchers analyzed biopsy samples from 58 patients before treatment, discovering overproduction of Gal-1 in tumors that recurred rapidly. Further experiments using cell cultures and mouse models confirmed that Gal-1 enhances the ability of cancer cells to utilize sugar for energy even under thermal stress, thus supporting their survival and regrowth.

In exploring potential treatment improvements, the team tested a drug called OTX008, which inhibits Gal-1. When combined with ablation in mouse studies, this approach led to a twofold reduction in tumor size and decreased energy production within cancer cells. These promising results indicate that targeting Gal-1 could make thermal ablation more effective by reducing the likelihood of recurrence.

The findings point to the potential of combining Gal-1 inhibitors with conventional treatments to improve patient outcomes. In particular, this strategy could be beneficial for early-stage, unresectable liver cancer and may also enhance responses in more advanced cases. The research emphasizes the importance of understanding tumor metabolism and suggests that disrupting Gal-1 may not only improve thermal ablation efficacy but also broaden therapeutic options across different stages of liver cancer.

Overall, this discovery offers valuable insight into the metabolic mechanisms behind liver cancer resistance and recurrence. It underscores the potential of targeting specific proteins like Gal-1 to prevent tumor regrowth and improve long-term survival rates for patients undergoing heat-based cancer therapies.

Source: https://medicalxpress.com/news/2025-07-key-protein-liver-cancer-resist.html