ETH Researchers Disable Tumor Cells' Defense Mechanism

(CONNECT) Researchers at ETH have developed a light-controlled molecular switch that awakens lung cancer cells from a protective dormant state. Stress hormones can put tumor cells into a sort of dormant state via glucocorticoid receptors found in every cell of the body, explains ETH in a press release. However, for therapies to target cancer cells, those cells must be active.

For their approach, the researchers used light and a kind of the body's own recycling system. The latter marks defective proteins, which are then broken down by the cell. Here, the glucocorticoid receptors on the tumor cells were labeled. The light was used to prevent the receptors in the surrounding healthy tissue from being affected as well.

Specifically, the researchers have developed a three-part switch. It consists of two subunits that bind to the receptor and the labeling enzyme, respectively, with a flexible linker between them. If this link is straight, the enzyme can mark the receptor for degradation. If it is denatured by exposure to light of a specific wavelength, the enzyme cannot reach the receptor.

In laboratory cultures of lung cancer cells, the researchers were able to use their method to deactivate the tumor cells' receptors, thereby bringing the cells out of dormancy. Switches that migrate from tumor cells into healthy tissue were selectively deactivated using light. “This allows the activity to be strictly confined to the tumor core, thereby sparing the surrounding tissue and resulting in significantly fewer side effects,” research group member Robin Scheuplein is quoted as saying in the press release. “The effect is reversible and can be precisely controlled.” ce/hs