A new study found that combining histone deacetylase inhibitors, poly (ADP ribose) polymerase inhibitors, and decitabine resulted in synergistic cytotoxicity in all cell lines tested. This combination impaired DNA repair pathways and altered epigenetic regulation of gene expression.
Researchers found that DNA damage accumulates in arteries with aging and contributes to impaired vascular function. In mice lacking or heterozygous for the double-strand DNA break repair protein ATM kinase, aging accelerated vascular dysfunction, including increased arterial stiffness and oxidative stress.
Scientists at Max Delbrück Center discovered two lead compounds that inhibit activation of IKK/NF-κB pathway only when triggered by DNA double-strand breaks. These substances make cancer cells more sensitive to chemotherapy, potentially increasing the success rate of genotoxic cancer therapies.
A study by Dana-Farber Cancer Institute researchers found that inhibiting the ATM protein can kill tumor cells with dysfunctional DNA repair pathways. Individuals with one mutant copy of a key gene are also at increased risk of developing cancer, as their remaining gene becomes mutated in specific cell types.