"The virus appears to be regulating the expression of genes that control all of the characteristics of hypoxic tumors, those that promote survival, drug resistance and the spread of the cancers," Rettig said. "It's good for the tumor, bad for the patient."
In HPV-associated cancers, the HPV DNA is integrated into the cancer cell's genome, where it expresses a protein called E6. In the cancer cell's hypoxic environment, the protein targets a cell signaling pathway called NF-B, heightening its activation, Rettig said. This is the first time an association has been shown between the virus and hypoxia-induced activation of the cell signaling pathway.
The findings in the study happened by coincidence, Rettig said. He and his team were screening different cancer cell types for hypoxia-induced activation of the cell signaling pathway. When he looked at the results, Rettig noted that only the cancer cell types that were HPV-positive had heightened activation of the NF-B pathway. Cervical and head and neck cancers not caused by HPV did not have heightened activation of the pathway.
"The cells had to have the virus to have the activation," he said.
The next step for Rettig and his team is to confirm the findings in additional animal models to gain broader understanding of the potential correlation of hypoxia and activation of the cell signaling pathway in humans. He hopes to have a drug to test in human clinical studies in about five years.
HPV is the most common sexually transmitted disease in the world. About 20 million Americans currently are infected with HPV, according to the Centers for Disease Control, and another 6.2 million people become newly infected each year. At least 50 percent of sexually active men and women will acquire genital HPV infection at some point in their lives.
In addition to cervical and head and ne
|Contact: Kim Irwin|
University of California - Los Angeles