The 'zombie cell' effect

Researchers have identified a biological mechanism that helps explain why some lung and ovarian cancers become resistant to chemotherapy, offering insight into why cancers recur.

The study, published in Nature Aging this month, investigated how platinum-based chemotherapies such as cisplatin negatively affect tumour behaviour in non-small cell lung cancer (NSCLC) and high-grade serous ovarian cancer (HGSOC). Although these treatments are widely used, their long-term effectiveness is often limited when tumours return or stop responding.

Professor Ljiljana Fruk and Muhamad Hartono from the Department of Chemical Engineering and Biotechnology (CEB) contributed to the international collaboration, led by researchers from the Early Cancer Institute and the Cancer Research UK Cambridge Institute. Their involvement follows her Bionano Engineering group's recent development of a urine test for early lung cancer detection.

The researchers found that platinum chemotherapy can push a subset of cancer cells into senescence – a state in which cells remain alive but no longer divide. These so-called ‘zombie cells’ release TGFβ, a signalling molecule that helps nearby cancer cells survive, grow, and resist treatment. Analysis of patient data supported these observations, showing that tumours displaying features of senescence after platinum treatment were linked to poorer outcomes in both lung and ovarian cancers.

The tumour-promoting response was most pronounced with platinum chemotherapy. While drugs such as docetaxel and palbociclib also induced senescence, they did not trigger the same TGFβ-enriched SASP. The study also found that age influenced treatment response, with tumours in middle-aged animals growing more readily than in younger mice, suggesting that the combined impact of ageing and treatment-related damage may shape conditions for cancer progression.

Encouragingly, either blocking TGFβ signalling from senescent cells, or removing the cells using senolytic treatment, prevented the tumour-promoting effects of therapy-induced senescence. The findings indicate that combining platinum-based chemotherapy with therapies that target senescent cells or their signalling pathways could represent a promising direction for improving treatment effectiveness.

Prof Fruk said the work advances understanding of the biological processes that sit behind treatment resistance.

“By clarifying how surviving senescent cells influence tumour growth, this research helps identify potential intervention that could help to shape health strategies that ultimately reduce recurrence,” she said.

“Senescence is increasingly recognised as an active component of cancer biology rather than a passive treatment by-product. Studies like this are important for connecting mechanistic insight with opportunities for therapeutic innovation.”

The authors emphasise that further clinical research will be needed before these approaches influence patient care. However, identifying a targetable driver of chemotherapy resistance marks an important step towards more precise treatment strategies.