EXO1 gene overproduction may reveal cancer treatment target
5 reported2 unconfirmed
Researchers at Penn State College of Medicine have found that excessive activity of the DNA repair gene EXO1 can damage DNA rather than protect it, according to a study published in Nature Communications. The team discovered that EXO1 is overexpressed in 20% to 30% of breast and ovarian cancers, as well as in melanoma, testicular, cervical and hepatobiliary cancers. Cancer cells with high EXO1 levels behaved similarly to cells with BRCA mutations, even when no BRCA mutation was present. The researchers tested the drug olaparib, commonly used against BRCA-mutant cancers, and found that tumors with elevated EXO1 were highly sensitive to the treatment. They also found that EXO1-overexpressing tumors responded to the chemotherapy drug cisplatin. The study’s senior author stated that EXO1 could potentially serve as a biomarker to help predict which patients are more likely to respond to certain chemotherapy treatments. The research was supported by funding from the National Institutes of Health and Four Diamonds.
What’s reported
The study was published in Nature Communications and conducted by researchers at Penn State College of Medicine.
EXO1 is overexpressed in 20% to 30% of breast and ovarian cancers, as well as in melanoma, testicular, cervical and hepatobiliary cancers.
Excess EXO1 destabilizes newly formed DNA by expanding single-stranded DNA gaps and degrading reversed replication forks.
Tumors with elevated EXO1 responded to olaparib and cisplatin similarly to BRCA-mutant cancers.
The research team plans to continue studying EXO1 with the goal of launching clinical trials.
Open questions
Whether EXO1 overexpression directly causes cancer.
Whether clinical trials will confirm the biomarker’s usefulness in treatment decisions.
Key figures
George-Lucian Moldovan, professor of molecular and precision medicine and senior author on the study.
Alexandra Nusawardhana, lead author of the study.
Claudia Nicolae, assistant professor of molecular and precision medicine at Penn State College of Medicine.
Sources: ScienceDaily
