When it comes to cancer, tumor suppressor genes are usually thought of as the "good guys." These genes make proteins that protect and repair DNA in cells. If they stop functioning or there's not enough, cancer risk goes up. But there can be too much of a good thing: When cells overexpress the gene EXO1 - meaning that they make more of the protein than they should - it can degrade the DNA it's supposed to repair. This causes damage that can disrupt the genome, which is a hallmark of cancer, according to a team of researchers from Penn State College of Medicine.
In a study published in Nature Communications, the researchers found that the EXO1 gene is overexpressed in 20% to 30% of breast and ovarian cancers as well as in melanoma, testicular, cervical and hepatobiliary cancers, which develop in the liver, gall bladder and bile duct. Tumor cells with high levels of EXO1 protein exhibit characteristics similar to cells with a BRCA mutation, a genetic code change known for its link to hereditary breast and ovarian cancers. That means that these tumor cells behave like BRCA-mutant cells - including their response to the chemotherapies and other drugs - even when there is no BRCA mutation present, a finding the researchers said hasn't previously been established.
"EXO1 doesn't predict cancer risk, but it could potentially serve as a biomarker to help predict which patients are more likely to respond to certain chemotherapy treatments, leading to more personalized therapies," said George-Lucian Moldovan, professor of molecular and precision medicine and senior author on the study. "The same drugs that are reserved for treating BRCA-mutant tumors and that have fewer side effects could potentially be used to treat EXO1 overexpressing tumors, which don't have BRCA mutations. It would expand the applicability of those drugs."
