Inside every human cell, tiny repair systems work to fix damaged DNA. However, sometimes these systems malfunction. Researchers at Penn State College of Medicine have found that when cancer cells produce too much of a repair protein called EXO1, it stops fixing the cell and starts destroying it. This self-destruction creates a weakness that could be used to treat many types of tumors with existing medicines, according to a 2026 study in Nature Communications.
The discovery focuses on how EXO1 works when there is too much of it. The research team, led by George-Lucian Moldovan, discovered that high amounts of this protein cause serious damage to chromosomes. Instead of repairing DNA, the extra protein attacks new DNA. It specifically targets and breaks apart genetic material.
To confirm this, scientists created a version of EXO1 that could not cut DNA. When they used this modified protein in lab tests on human cancer cells, the destruction stopped. This proved that the protein's cutting ability was causing the damage.
Alexandra Nusawardhana, the study's lead author, explained that too much EXO1 creates harmful DNA problems. She believes this makes tumors more sensitive to chemotherapy and increases cell death. This sensitivity is promising because tumors with too much EXO1 become similar to cells with a BRCA mutation, which are known to be linked to hereditary cancers. Even without BRCA mutations, these tumors show the same weaknesses.
Because they act like BRCA-mutated cells, these tumors respond well to the same treatments. Cancers with high EXO1 levels were more sensitive to cisplatin, a common chemotherapy drug, and olaparib, a targeted drug usually for BRCA-mutant cancers. Moldovan stated that using these drugs for EXO1-overexpressing tumors could expand their use.