A new study shows that cancer damages its own DNA by pushing key genes to work too hard.
Cancer cells grow by turning certain genes on at extremely high levels, especially genes that help them multiply. But the study suggests that this frantic activity comes with a cost: it can physically damage the cell’s DNA.
The research, published in Science Advances, was led by PhD student Osama Hidmi under the guidance of Rami Aqeilan of the Hebrew University of Jerusalem and reveals an overlooked source of genetic instability in cancer. The team found that DNA breaks in cancer cells often occur in the same places where the disease is pushing growth genes the hardest. The focus was on super-enhancers, stretches of DNA that act like powerful control panels, boosting the activity of nearby genes and keeping cancer-driving programmes running at full volume.
Using a sensitive genome-mapping approach, the researchers generated detailed maps of double-strand breaks, one of the most serious kinds of DNA damage, in which both strands of the DNA molecule snap. The breaks were not random: they cluster within genes driven by super-enhancers, suggesting that when cancer forces certain genes to run nonstop, it can strain the system enough to trigger breaks.
The team also tracked a natural “alarm” signal cells use to flag DNA damage and bring in repair crews. They found that cancer cells repeatedly break and repair DNA in these high-activity regions. While this helps tumours survive, frequent repair can raise the chance of small mistakes, making these sites more likely to accumulate new mutations over time.
“Cancer cells rely on super-enhancers to keep growth genes running at high speed,” Aqeilan said.
“What we found is that this same high-output activity can put real strain on the DNA, creating break hotspots that the cell has to repair again and again. That cycle may help tumours survive in the short term, but it also increases the risk of mutations that can fuel cancer’s evolution.”
Hidmi said: “What is especially exciting, because cancer cells depend on these high-stress DNA regions to keep growing, they may also be more vulnerable there. This opens the door to treatments that target the very processes tumours rely on to survive.”
DNA damage and repair are central to how cancers grow, change, and resist treatment. This study helps explain where some of the most important damage happens and why. By showing that cancer’s strongest gene-control regions are also sites of repeated DNA stress, the research points to potential weak spots in tumours, areas that may be especially sensitive to treatments that disrupt runaway gene activity or interfere with DNA repair. Understanding this process could help researchers design strategies that make it harder for cancer to adapt and evolve.
By revealing how cancer’s drive to grow can destabilize its own DNA, the study adds an important piece to the puzzle of why tumours are both aggressive and genetically unstable, and how that instability might eventually be used against them.