Hungarian scientists uncover how "zombie" cancer cells resist chemotherapy and fuel relapse in breast cancer

For decades, therapy-induced senescence (TIS) was believed to be an irreversible process, forcing damaged cells into a permanent state of dormancy before eventual removal. However, by mapping the single-cell transcriptome of TIS cells in an unprecedented way, the Hungarian team revealed that cancer cells can escape this supposedly final stage and initiate tumor regrowth.

Alarmingly, this "zombie mode" also conferred resistance to half of the FDA-approved drugs tested, transforming TIS from a mechanism of cellular shutdown into a full-fledged survival strategy. The findings, published in Molecular Cancer, signal both a promising avenue for the development of therapies targeting TIS cells and a stark warning for clinicians: relying on TIS as a therapeutic endpoint could backfire, as cancer cells may break free while simultaneously resisting multiple other drugs.

“It’s a truly paradoxical situation - what we thought was an ally in cancer treatment has actually been a hidden adversary all along,” said Eszter Bajtai, first author of the study, who spent six years on the project. “In our experiments, if cancer cells entered TIS, some escaped within months - virtually every time. It was exciting, but also terrifying.”

Beyond their remarkable drug resistance, the team uncovered another startling revelation: the relationship between zombie cells and the immune microenvironment. Normally, senescence in healthy cells triggers an immune response that removes them. However, TIS cancer cells take a different approach - actively suppressing immune attacks by activating specific pathways and expressing immune-dampening proteins. This means zombie cells are not only impervious to chemotherapy and targeted biological therapies, but also capable of evading the body's natural defenses.