CINCINNATI – A protein in the cell nucleus already targeted therapeutically for several types of cancer has now been linked to an aggressive form of pediatric liver cancer called hepatoblastoma (HBL), according to a study published in the Nature journal Communications Biology.
Scientists at Cincinnati Children’s Hospital Medical Center conducted extensive biological and genetic tests on donated HBL tumor samples and found highly elevated levels of the protein PARP1 in patients with this cancer. PARP1 modifies chromatin structure in the cell nucleus to drive the chemotherapy-resistant form of liver cancer, according to the study’s lead investigator, Nikolai Timchenko, PhD, head of the Liver Tumor Biology, Liver Tumor Program.
An FDA-approved drug called Olaparib that blocks PARP1 is already used to treat other types of cancer. In their tests on human liver tumor cells, Timchenko and colleagues learned that PARP1 binds to DNA regions within many cancer-related genes and activates their expression in (HBL) to drive the disease. When the researchers pharmacologically blocked PARP1 in the tumor cells, this slowed or stopped cancer progression.
“Our findings provide a strong rationale for testing PARP1 inhibitors to treat aggressive pediatric liver cancer, but additional research is needed before we can verify this
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