To test their theory, Wang and his colleagues treated mice that had cancerous tumors with a molecule to inhibit the PAD4 enzyme. They found that, especially when combined with additional enzyme inhibitors, the treatment worked as effectively as the most-commonly-used chemotherapy drug, doxorubicin, which shrinks tumors by about 70 percent.
Most striking, however, was that the PAD4 enzyme-inhibition strategy caused significantly less damage to healthy tissues. "Current chemotherapy drugs such as doxorubicin don't attack just tumors; unfortunately, they also attack healthy areas of the body," Wang explained. "That's why chemotherapy patients experience such terrible side effects such as weight loss, nausea, and hair loss. Because the PAD4 treatment appears to be less toxic, it could be an excellent alternative to current chemotherapy treatments."
Wang also explained that the PAD4 gene's dual personality -- on the one hand a helpful defense against bacteria, while on the other, a harmful silencer of cancer-suppressor genes -- can be understood from the perspectives of evolution and longer life spans. "Our ancestors didn't have antibiotics, so a bacterial infection could easily result in death, especially in young children," Wang explained. "So, back then, an overactive PAD4 gene was advantageous because the NET bacteria-trapping mechanism was the body's major defense against infection." Wang also explained that on the other hand, because people today have access to antibiotics, we live much longer than our ancestors did. "PAD4's bad effects -- cancer and autoimmune diseases -- tend to be illnesses that appear later in life," Wang said. "So nowadays, an overactive PAD4 gene, while still protective against bacteria, can
|Contact: Barbara Kennedy|