Cancer: exploiting the weakness of “zombie” cells to better treat tumors

By Elodie Vaz | Published on May 4, 2026 | 4 min read


In most cancers, not all tumor cells actively proliferate. A fraction enters senescence, a state of durable arrest of cell division. Often referred to as “zombie” cells, these cells remain metabolically active without multiplying. Long considered beneficial, senescence is indeed one of the mechanisms through which chemotherapy slows tumor growth.  

However, this protective status has a downside. Senescent cells secrete a range of pro-inflammatory and pro-tumoral molecules capable of reshaping their microenvironment. They thereby promote the proliferation of neighboring cells, metastasis, and the recruitment of harmful immune cells. They are also involved in age-related conditions such as fibrosis.

“Senescence has long been viewed as a positive phenomenon because senescent cells do not proliferate, unlike the main hallmark of cancer,” recalls Mariantonietta D’Ambrosio, postdoctoral researcher at the MRC Laboratory of Medical Sciences (LMS) and first author of the study published on April 24 in Nature Cell Biology, in a press release. “However, over time, senescent cells also display negative aspects.”

Identifying a new therapeutic vulnerability

In light of this, researchers from LMS and Imperial College London are seeking to identify molecules capable of selectively eliminating these senescent cells, known as senolytics. Their strategy is based on a recently described weakness: the increased sensitivity of senescent cells to ferroptosis, a form of cell death triggered by the accumulation of iron and reactive oxygen species.  

“Recent studies have highlighted this predisposition of senescent cells to ferroptosis, but this represents a new vulnerability linked to senescence. This gives us an opportunity to exploit,” emphasizes Mariantonietta D’Ambrosio.

Glutathione peroxidase 4: a key target

To exploit this weakness, the researchers conducted a large-scale pharmacological screening. In collaboration with the Department of Medicinal Chemistry at Imperial College London, they focused on a class of molecules known as “covalent compounds,” which can bind durably to their protein targets and inhibit proteins previously considered difficult to drug.

A total of 10,000 covalent compounds were tested on senescent cells and normal cells, with the aim of identifying molecules that preferentially destroy the former. Four promising candidates emerged. Three of them targeted the same protein: glutathione peroxidase 4 (GPX4).  

This enzyme protects cells against ferroptosis. Senescent cells, exposed to high levels of iron and oxidative stress, overexpress GPX4 to survive. By inhibiting this protection, the identified compounds make ferroptosis inevitable.  

The researchers compare this mechanism to taking painkillers preventively to keep running with a sprain. The danger remains, but the symptoms are masked. Removing the analgesic abruptly reveals the underlying fragility.  

The team then evaluated these molecules in three distinct mouse models of cancer. In each case, eliminating senescent cells resulted in reduced tumor size and improved survival. “In mouse models, we observed that these drugs reduced tumor size and improved survival,” explains Professor Jesus Gil, senior author of the study and head of the Senescence group at LMS.  

Researchers are now seeking to better understand the immunological impact of this strategy. “Does this improvement also stimulate beneficial immune cells (T lymphocytes, NK cells) that contribute to tumor destruction?” he asks.

A complementary approach to chemotherapy and immunotherapy

Beyond proof of concept, this study paves the way for more personalized medicine. Patients whose tumors overexpress GPX4, particularly after chemotherapy, could be good candidates for combination therapies.  

“Targeting senescence represents a tremendous opportunity for cancer treatment and could ultimately serve as a supportive approach alongside chemotherapy and immunotherapy,” concludes Mariantonietta D’Ambrosio.  

The next step will be to confirm these findings in humans and to identify the tumors most likely to benefit from this approach, at the intersection of oncology and aging biology.




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About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans