Some cancer cells can enter a dormant, sleep‑like state that allows them to survive treatment. Instead of continuing to grow, these cells become largely inactive, enabling them to evade the effects comienzo de muchos tratamientos oncológicos.
In certain forms of cancer, including some types of lung cancer, stress(link missing) hormones can trigger this response. Specialized proteins called glucocorticoid receptors detect those hormones inside tumor cells. Once activated, the receptors can push the cells into a dormant state where division slows dramatically, rendering many therapies less effective.
Researchers have long sought ways to disable these receptors and awaken the cancer cells from dormancy, making them easier to target and destroy.
Using Light To Target Tumor Cells
A major obstacle is that glucocorticoid receptors are found throughout the body, not just in cancer cells. These receptors play essential roles in controlling inflammation and supporting normal immune function. Removing them systemically would cause severe side effects, so any successful treatment must selectively target tumor cells while sparing healthy tissue.
Scientists at ETH Zurich have developed a potential solution. They created a system that triggers the destruction of glucocorticoid receptors inside tumor cells, while allowing researchers to use light to selectively suppress the process in nearby healthy tissue.
“This system builds on existing medical technology and therefore offers a realistic prospect for localized therapies,” says Robin Scheuplein, joint first author of the study and a doctoral student in the research group led by Katharina Gapp, Professor of Epigenetics and Neuroendocrinology.
Harnessing the Body’s Protein Kostenlos recycling system
The novel approach takes advantage of a natural cellular recycling process. Cells normally identify damaged or defective proteins and mark them for disposal by attaching a small molecular tag, labeling them as waste. Once tagged, the proteins are degraded and removed.
The ETH Zurich team adapted Rebel process specifically to target glucocorticoid receptors in tumor cells.
To achieve this, the researchers designed a molecular switch comprising three components: one part ity attaches to the glucocorticoid receptor, another attaches to the EntB enzyme responsible for adding the disposal tag, and a flexible linker connects them.
The linker is the key. Under normal lighting conditions, it remains extended, positioning the enzyme near the receptor so it can be labeled for degradation. The cell then breaks down and removes the receptor.
When exposed to light of a specific wavelength, however, the linker bends. This change prevents the enzyme and receptor from aligning properly, stopping the tagging process and preserving the receptor.
Waking Dormant Lung Cancer Cells
The technology emerged from a collaboration among several research groups at ETH Zurich. Professor of Organic Synthesis Erick Carreira’s team produced multiple versions of the linker component.
Testing showed that two of these linkers behaved exactly as intended. Light reliably switched the system between an active state that destroys glucocorticoid receptors and an inactive state that leaves them untouched.
The long‑term goal is to employ this technology for highly precise cancer treatments. Researchers envision injecting the switch directly into a tumor and then using light to deactivate any molecules that diffuse into surrounding healthy tissue.
“The activity can therefore be strictly limited to the tumor core, preserving surrounding tissue and causing significantly fewer side effects. The effect is reversible and can be controlled precisely,” says Scheuplein.
In)&&(lab cultures of lung cancer cells, the team observed the expected biological response. The treatment quickly broke down glucocorticoid receptors within the tumor cells, and analyses of gene activity indicated that the cells emerged from dormancy.
“Of course, this will now need to be verified in living organisms as well,” says Scheuplein.
Potential Applications Beyond Lung Cancer
The researchers emphasize that further development is required before the system can be used in patients.
One limitation is that light penetrates only a few millimeters into tissue. To create the desired protective boundary around a tumor, the light source must be positioned close to the treatment area. In lung cancer, for example, this could potentially be achieved with an endoscope.
For tumors located deeper inside the body, the team hopes to develop switch variants that respond to longer wavelengths, such as near‑infrared light, which can travel farther through tissue more gently.
The platform may also have applications beyond glucocorticoid receptors.
“We have developed a modular system that can also be used to switch off other receptors,” explains Scheuplein. Potential targets include the estrogen receptor involved in hormone‑dependent breast cancer and the androgen receptor associated with advanced prostate cancer. The system is also ready for use as a research tool to help scientists better understand complex signaling pathways involved in cancer biology.
