A population of cells that initiates its own programmed death and then reverses course, surviving to rebuild damaged tissue, sits at the heart of a new study from the Weizmann Institute of Science, and the same mechanism, researchers say, may help explain why some tumours return after radiation therapy in a harder-to-treat form. The paper focuses on what its authors call DARE cells cancer resistance, a cellular survival behaviour that has not previously been characterised at the molecular level.
The study was published in Nature Communications on 4 December 2025, according to SciTechDaily, resolving a puzzle that has lingered since the 1970s. That was when researchers first observed that fruit fly larvae, despite severe radiation damage to epithelial tissue, could regenerate fully functional wings. The response was named compensatory proliferation. How cells managed to drive such dramatic regrowth remained unexplained for roughly half a century.
What DARE cells actually do
To investigate, a team led by Dr Tslil Braun from the laboratory of Prof. Eli Arama recreated that original experiment, exposing fruit fly larvae to ionising radiation but using modern genetic tools to track tissue regeneration in much finer detail. The researchers were looking for cells that had switched on their self-destruct machinery but had not followed through.
They found them. The team named them DARE cells, cells in which the initiator caspase, an enzyme that starts the apoptosis cascade, had been activated but that had nonetheless survived irradiation. The company does not claim this is the whole story, and the paper is careful to describe a mechanism, not a cure. What the data show is striking enough on its own terms: DARE cells multiplied, repaired damaged tissue, and replenished nearly half of it within 48 hours, according to Braun.
The other half came from a second population the researchers identified and named NARE cells. Unlike DARE cells, NARE cells’ initiator caspase had never been activated. The two populations are not interchangeable. When DARE cells were removed from the experimental system, compensatory proliferation disappeared entirely, the team reports, suggesting DARE cells are the indispensable driver of the response. DARE cells, Braun explains, were themselves activated by signals from dying neighbouring cells.
DARE cells cancer resistance and the inheritance of survival
The molecular explanation for how DARE cells survive involves a stalling of the death pathway. The initiator caspase switches on, but a motor protein tethers it to the cell membrane, preventing it from activating the executioner caspases that would complete cell destruction. Arama notes that overactivation of that same motor protein has previously been linked to cancerous tumour growth, which the team says suggests it may be one mechanism by which cancer cells evade apoptosis.
The clinical resonance of that finding is direct. Radiation therapy and many other conventional cancer treatments work by pushing tumour cells into apoptosis. If a subpopulation of those cells can stall the process partway through, they survive. The researchers then asked whether that survival conferred any lasting advantage.
The answer, based on their experiments, is that it does. When the same tissue was irradiated a second time, the number of cells that died in the first few hours was half that seen after the first irradiation. Most of the dead cells in that second round belonged to the NARE population. Descendants of DARE cells were found to be seven times more resistant to cell death than cells in tissue that had never experienced the initial radiation exposure. Arama says this may help explain why recurrent tumours become more treatment-resistant after radiation.
The research also identified a feedback mechanism governing the process. DARE cells appear to promote the growth of nearby NARE cells by secreting growth signals; NARE cells, in turn, secrete signals that inhibit DARE cell growth. The team describes this as a negative-feedback loop that prevents overgrowth during tissue repair.
It is worth noting the study’s scope before drawing broad conclusions. The experiments were conducted in fruit fly larvae. Arama acknowledges that additional research will be needed to determine how closely the same mechanisms operate in humans, though fly models have repeatedly helped uncover fundamental biological processes with parallels across species, including in humans.
Funding for the work came from the Israel Science Foundation (grant No. 1378/24) and from the European Research Council under the EU’s Seventh Framework Programme, according to the SciTechDaily report on the paper. Collaborators included researchers from UMass Chan Medical School and the Severo Ochoa Molecular Biology Center in Spain.
Arama frames the dual implication plainly: understanding how DARE cells escape death could point toward ways of accelerating healthy tissue repair after injury, while the same knowledge could reveal why cancer treatments sometimes fail and how they might be improved. The next step, he says, is translating what fly models have shown into an understanding of growth control and death resistance in human epithelial cells, where many cancers originate.
