Scientists have found a hidden weakness in an aggressive form of kidney cancer that could point to a new combination treatment, according to research published in the Proceedings of the National Academy of Sciences.

The study, led by Xin Lu at the University of Notre Dame, focused on clear cell renal cell carcinoma. This cancer often carries a change in a gene called VHL, a tumour suppressor.

The team found that losing VHL activates a protein called HIF-2-alpha. This makes the cancer cells produce large amounts of another protein, TRAIL. TRAIL normally tells damaged cells to destroy themselves by locking onto “death receptors” on the cell surface.

But too much TRAIL had an unexpected effect. The death receptors became trapped inside the cells, where outside treatments could not reach them.

The researchers then tested belzutifan, an approved kidney cancer drug that blocks HIF-2-alpha. It lowered TRAIL levels and let the trapped receptors move back to the surface. Adding lab-made TRAIL then triggered much more cancer cell death.

The findings come from laboratory and model studies. More work is needed before this becomes a treatment.