Light controlled therapy exposes cancer cells hiding from chemotherapy

A quiet survival trick allows some cancer cells to outlast even the most aggressive treatments. Instead of dying, they slip into a dormant state, barely dividing and effectively hiding from drugs. Now, scientists at ETH Zurich have developed a way to wake those cells up, using light to target a key mechanism that controls this sleep-like behavior.

Their findings offer a new approach to cancer therapy, one that could make resistant tumors vulnerable again while protecting healthy tissue.

In several cancers, including certain lung tumors, stress hormones can trigger a powerful defense. These hormones activate proteins inside cells called glucocorticoid receptors. Once activated, these receptors push cancer cells into a low-activity state.

In this state, cells stop dividing. Many treatments, especially chemotherapy, target fast-growing cells. When growth slows, those therapies lose their effectiveness. The result is a population of cells that survive treatment and may later restart the disease.

Scientists have long tried to block these receptors. The idea is simple. If the receptors are removed, the cells may leave dormancy and become easier to destroy. The challenge lies in the fact that every cell in the body uses these receptors.

They play critical roles in controlling inflammation, supporting immune responses, and managing stress. Removing them everywhere would cause serious harm.

Researchers at ETH Zurich have designed a system that solves this problem with precision. Instead of blocking receptors throughout the body, their method removes them only inside tumors.

The system relies on a light-controlled molecular switch. This switch determines whether glucocorticoid receptors are marked for destruction.

Robin Scheuplein, a doctoral researcher involved in the work, explained the approach. “This system is based on existing medical technology and therefore offers a realistic prospect of localised therapies,” he said.

The idea centers on controlling where the system is active. By using light, scientists can switch off the effect in surrounding healthy tissue while keeping it active in the tumor itself.

Cells already have a built-in process for removing unwanted proteins. When a protein is damaged or no longer needed, the cell attaches a small chemical tag to it. This tag acts like a signal for disposal. The protein is then broken down and recycled.

The research team adapted this natural system. They created a three-part molecule designed to guide the disposal of glucocorticoid receptors.

One part binds directly to the receptor. Another connects to the enzyme that adds the disposal tag. Between them sits a flexible linker, which acts as the switch.

Under normal conditions, the linker stretches into a shape that allows the enzyme to reach the receptor. The tagging process occurs, and the receptor is destroyed.

When exposed to a specific wavelength of light, the linker changes shape. It bends in a way that prevents the enzyme from reaching the receptor. Without tagging, the receptor remains intact.

This simple shift allows precise control. Scientists can decide when and where receptors are removed.

The team tested the system in laboratory cultures of lung cancer cells. The results showed that the active form of the molecule rapidly reduced glucocorticoid receptor levels.

As those receptors disappeared, the cells began to change. Genetic analysis revealed that the cells left their dormant state and resumed activity.

This shift is important. Once cells begin dividing again, they become more vulnerable to existing treatments. The approach does not kill the cells directly. Instead, it removes their protective state.

Scheuplein described the significance. “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,” he said.

The use of light adds a critical layer of safety. Light can be directed with high accuracy, allowing doctors to control exactly where the treatment is active.

In practice, the molecule would be delivered into a tumor. Light would then be applied to the surrounding area to deactivate any molecules that move beyond the target. This creates a protective boundary around healthy tissue.

Because light penetration is limited, the method works best when the source can be placed close to the tumor. In lung cancer, for example, an endoscope could deliver light directly to the affected area.

For tumors located deeper in the body, researchers are exploring new versions of the system. These would respond to longer wavelengths, such as near-infrared light, which can travel further through tissue.

The system is not limited to one type of receptor. Its modular design allows scientists to adapt it for other targets.

Scheuplein noted this potential. “We’ve developed a modular system that we can also use to switch off other receptors,” he said.

This opens the door to new applications. Hormone-driven cancers, such as certain breast and prostate cancers, rely on different receptors. By adjusting the molecule, researchers could target those pathways as well.

The system could also serve as a research tool. By turning specific proteins on and off with light, scientists can study how cancer cells respond in real time.

While the results are promising, the work remains in early stages. The experiments so far have been conducted in cell cultures. The next step is to test the system in living organisms.

Researchers must also refine the technology. They aim to improve how efficiently the molecules target receptors and how precisely they respond to light.

Another challenge involves delivering light deep into the body. Advances in medical imaging and minimally invasive tools may help overcome this limitation.

Despite these hurdles, the concept represents a significant shift. Instead of attacking cancer cells directly, the strategy removes their defenses and lets existing treatments do the rest.

This approach highlights a broader change in cancer research. Scientists are moving toward therapies that are more precise and adaptable. Rather than affecting the entire body, treatments can be focused on specific cells and pathways.

The ability to control these processes with light adds a powerful tool. It allows treatments to be turned on and off as needed, reducing unwanted effects.

By targeting dormancy, the research addresses one of the most persistent challenges in oncology. It offers a way to prevent cancer cells from hiding and returning later.

This discovery could change how doctors approach resistant cancers. By waking dormant cells, the method may make existing therapies more effective. This could reduce the risk of relapse and improve long-term outcomes.

The technology also offers a safer way to target important cellular pathways. Because the treatment can be controlled with light, it limits damage to healthy tissue. This may reduce side effects compared to broader therapies.

In the future, similar systems could be used to target other proteins involved in disease. This includes pathways in hormone-driven cancers and other conditions where precise control is needed.

Beyond treatment, the approach could help researchers study how cancer behaves. By switching specific proteins on and off, scientists can gain deeper insight into how tumors grow and resist therapy.

As the technology develops, it may lead to more personalized treatments. Doctors could tailor therapies to individual patients, activating them only where and when needed. This level of control could mark a major step forward in cancer care.

Research findings are available online in the journal Proceedings of the National Academy of Sciences.

The original story "Light controlled therapy exposes cancer cells hiding from chemotherapy" is published in The Brighter Side of News.

Like these kind of feel good stories? Get The Brighter Side of News' newsletter.