Krebs: Wie „Zombie-Zellen” Tumore zurückbringen – und was sie jetzt stoppt – WELT

Researchers have identified a specific vulnerability in senescent cells, often referred to as zombie cells, which can contribute to cancer recurrence following therapy. These cells, which remain in the body after successful treatment, have been found to depend on a particular enzyme for survival, offering a potential target for new therapeutic interventions.

While chemotherapy can effectively stop the growth of tumors, some cells do not disappear entirely. Instead, they enter a state of senescence where they stop dividing but remain metabolically active. These senescent cells can fuel inflammation and create an environment that encourages the return of tumors.

Until now, these cells were considered difficult to target. However, a study published in the journal Nature Cell Biology indicates that these cells possess a critical weakness related to how they manage oxidative stress.

The Role of the GPX4 Enzyme

The survival of senescent cells is tied to an enzyme known as GPX4. This enzyme acts as a protective shield, preventing oxidative damage by stopping the accumulation of aggressive lipid degradation products within the cell membrane.

For healthy cells, this protection is beneficial. For senescent cells, it is essential for survival. This is because zombie cells exist under a state of constant stress, producing higher levels of reactive oxygen molecules, accumulating iron, and altering their lipid metabolism.

Because of these internal conditions, senescent cells are naturally predisposed to a specific type of cell death that healthy cells are better able to avoid.

Inducing Ferroptosis

The specific form of cell death that targets these cells is called ferroptosis. This process occurs when iron and oxidized lipids destroy the cell membrane, leading to the collapse of the cell.

Under normal circumstances, the GPX4 enzyme prevents ferroptosis from occurring. By inhibiting this enzyme, researchers can remove the protection that keeps zombie cells alive, effectively triggering the ferroptotic process and eliminating the cells that would otherwise promote tumor relapse.

Research and Compound Testing

To find a way to trigger this process, an international research team conducted large-scale testing on more than 10,000 chemical compounds. The goal was to determine which substances could specifically kill senescent cells without harming healthy tissue.

From this extensive screening, the researchers identified 38 compounds that were successful in targeting and eliminating these cells. These findings highlight the potential for developing targeted therapies that clear the body of senescent cells after cancer treatment to reduce the risk of recurrence.