Some tumour cells survive treatment by going to sleep. They stop dividing, and most cancer drugs, which work on cells that are growing, have little to grab. In certain lung cancers, stress hormones trigger the shutdown.
Researchers at ETH Zurich have now built a molecular switch that removes the trigger, and they can turn it off with light. In lab cultures of lung cancer cells it woke the dormant cells up. The work appeared in the Proceedings of the National Academy of Sciences on 21 May 2026.
The receptor problem
Inside the tumour cells, glucocorticoid receptors detect the stress hormones. Once activated, they push the cell into a state where division slows to almost nothing. Scientists have wanted to knock those receptors out and make the cells vulnerable again.
The catch is that every cell in the body carries glucocorticoid receptors. They help control inflammation and keep the immune system working. Removing them everywhere would cause disastrous side effects, so a treatment has to hit tumour cells and leave healthy tissue alone.
How the switch works
The team borrowed a disposal system cells already have. Cells attach a small molecular tag to damaged proteins, and tagged proteins get broken down. The researchers redirected that process to glucocorticoid receptors.
Their switch has three parts: one end that binds the receptor, one that binds the enzyme that applies the tag, and a flexible link between them. In normal light the link stays stretched, holding the enzyme at the right distance to tag the receptor. Under light of a given wavelength the link bends. Enzyme and receptor no longer line up, and nothing gets tagged.
The link was the hard part. Erick Carreira, professor of organic synthesis, and his group built several versions. Two behaved as intended in testing, flipping between a form that destroys the receptor and one that does not.
The plan is to inject the switch into a tumour, then shine light on the surrounding healthy tissue to disable any molecules that wander out. “Activity can therefore be strictly limited to the tumour core, preserving the surrounding tissue and causing significantly fewer side effects. The effect is reversible and can be controlled precisely,” said Robin Scheuplein, joint first author and a doctoral student in Katharina Gapp’s group. Gapp is professor of epigenetics and neuroendocrinology.
What has and has not been shown
In cultured lung cancer cells, the switch rapidly broke down the receptors, and gene activity showed the cells leaving dormancy. No animal or human data exist yet. “Of course, this will now need to be verified in living organisms as well,” Scheuplein said.
Light reaches only a few millimetres into tissue, so the source has to sit close to the tumour edge. For lung cancer an endoscope could do that. For deeper tumours the teams want switches that respond to longer wavelengths such as near-infrared, which travels farther and more gently.
Scheuplein described the system as modular, meaning other receptors could be targeted the same way. The oestrogen receptor in hormone-dependent breast cancer and the androgen receptor in advanced prostate cancer are candidates. The group says the tool is already usable in the lab for studying cancer signalling pathways.
Sources
- Light switch makes cancer vulnerable to attack
- Light switch wakes sleeping cancer cells and makes them vulnerable again
- A light-activated "switch" could wake dormant cancer cells and make them treatable again
