In a significant breakthrough for cancer treatment, Australian scientists have identified a crucial genetic mechanism that tumours use to hide from the body's own defences. This discovery of a molecular 'safety switch' could pave the way for a new generation of more potent immunotherapy drugs.
The Shield Protecting Cancer Cells
A team from the Olivia Newton-John Cancer Research Institute and the Walter and Eliza Hall Institute in Melbourne has pinpointed a specific gene, known as TAK1, that acts as a central hub for survival signals within cancer cells. Their research, published in the prestigious journal Cell Reports on Saturday, 20 December 2025, reveals how this gene helps tumours resist attacks from the immune system's killer T cells.
Lead researcher Dr Anne Huber, a postdoctoral fellow at ONJCRI and La Trobe University, explained that instead of dying when targeted by immune cells, cancer cells with active TAK1 activate a survival pathway. "It produces 'anti-death proteins' that allow the cells to withstand the assault," Dr Huber said. "We knew TAK1 helped cancer survive, but we didn't realise it was a key tactic to avoid immune system killing."
Switching Off the Defence
The research team used advanced gene-editing technology to deactivate the TAK1 gene in cancer cells during laboratory tests. The results were striking. Fellow researcher Tirta Djajawi reported that without this protective switch, "the tumour collapses under the force of immune attack."
This finding is crucial because modern immunotherapy treatments work by empowering the body's immune system to recognise and destroy cancerous cells. However, their effectiveness is limited for many patients whose tumours possess this innate protective shield. Associate Professor Conor Kearney, head of molecular immunology at ONJCRI, stated the work provides "ample opportunity to change the future of how we treat cancer." He added, "We've shown we can combine drugs with existing immunotherapy to begin to target it."
Focus on Melanoma and Future Steps
While the study was conducted across various cancer types, a primary focus was on melanoma, a cancer often treated with immunotherapy. Globally, about 330,000 people are diagnosed with melanoma each year. In Australia, the rates are particularly concerning, having risen from 53 cases per 100,000 people in 2000 to an estimated 70 cases in 2024, according to Cancer Council data. Melanoma caused an estimated 1,340 deaths in Australia in 2020.
The discovery that blocking TAK1 expression can significantly enhance immunotherapy's power offers a promising new direction. The Melbourne-based team now plans to explore practical ways to target the TAK1 gene in patients, with the ultimate goal of dramatically improving outcomes for people battling cancer.
