Researchers have developed a molecular switch that wakes lung cancer cells up from a protective dormant state so that they are more accessible for treatment. 

Tumour cells can lapse into a sleep-like state and thereby evade the destructive effect of cancer drugs. In some types of the disease, such as certain forms of lung cancer, this state is triggered by stress hormones in the body. Inside the cancer cells, glucocorticoid receptors recognise the hormones, and the cells respond by lapsing into a state in which they undergo barely any division. This renders many treatments ineffective.  

Researchers from ETH Zurich have developed a system that induces the destruction of these receptors. Light can be used to selectively neutralise the system’s effect in surrounding healthy tissue so that the impact is limited to the tumour.  

“This system is based on existing medical technology and therefore offers a realistic prospect of localised therapies,” says Robin Scheuplein, joint first author of the publication and a doctoral student in the research group led by Katharina Gapp, Professor of Epigenetics and Neuroendocrinology.  

In lab cultures of lung cancer cells, the researchers have succeeded in demonstrating the expected biological effect, with the active substance leading to a rapid breakdown of the tumour cells’ glucocorticoid receptors. An analysis of genetic activity also showed that the cells are woken from their dormant state as a result. 

As light only penetrates a few millimetres into tissue, the light source must be placed close to the tumour boundaries to establish the protective optical barrier. For deeper-seated tumours, the research teams want to develop switches that respond to longer wavelengths, such as near-infrared. 

Receptors of interest for clinical applications include the oestrogen receptor in the case of hormone-dependent breast cancer and the androgen receptor in advanced prostate cancer.