Researchers have identified a key enzyme – RNase H2 – that helps triple-negative breast cancer (TNBC) cells survive high levels of DNA replication stress. Because many breast cancer therapies work by causing replication stress, these results suggest RNase H2 is a promising treatment target. The study, led by Shiaw-Yih Lin, Ph.D., professor of Systems Biology, reveals that blocking RNase H2 directly damages cancer cell DNA while also activating the innate immune system to produce signals that attract T cells to attack the tumor.
“Adding RNase H2 inhibition is a one-two punch that overcomes the adaptive mechanism that triple-negative breast cancer tumors leverage to survive replication stress and continue progressing,” Lin said. “Our findings show that this is a promising therapeutic strategy that lays the groundwork to meaningfully improve patient outcomes for this aggressive and difficult-to-treat subtype of breast cancer.”