Blocking anti-viral enzyme could fight lung, pancreatic cancer
Blocking an anti-viral enzyme could lead to a new treatment for lung and pancreatic cancer suggest researchers who are testing a new synthetic compound in mice. The enzyme, TBK-1, plays an important role in immunity but is hijacked by pancreatic and non-small cell lung cancer that depend TPK-1 for growth and survival.
Compound 6-aminopyrazolopyrimidine tuns off TPK-1 in lab cells
The compound was found to turn off the enzyme action that promotes cancer in lab cells. The researchers from UT Southwestern Medical Center are testing a synthetic compound in mice to see if it can fight tumors. If successful, new drug treatment for lung and pancreatic cancer could emerge.
Dr. Michael White, professor of cell biology and senior author of the study published in the journal Molecular Cell said, “Our prediction is that TBK-1 is a good pharmacological intervention target for a subset of lung and pancreas cancers that are addicted to the activity of this enzyme. We believe there is a large population of cancer patients that could respond to inhibition of this activity.”
The research team looked at over 250,000 compounds, finding that 6-aminopyrazolopyrimidine can turn off the action of the TBK-1 enzyme that becomes mutated in 40 percent of lung cancers and 90 percent of pancreatic cancers.
In a 2006 UT news release published in the journal Cell, Dr. White said, "We got the surprise that this mechanism is involved in cancer cell survival, even though it's normally involved in immune response. We found something a little bit different — an Achilles' heel of cancer cells that's apparently broadly conserved among many types of solid tumors."
The pharmaceutical company Amgen has developed 6-aminopyrazolopyrmidine for ongoing study. The next step is to find out if the synthetic drug can penetrate small tumors in mice that the researchers say is important. The compound migrates to all other tissues.
The researchers say the next step is to verify the synthetic compound can be delivered to tumors. Blocking the TBK-1 enzyme with new drug therapy could stop cancer from spreading and destroy pancreatic and lung tumors.
Molecular Cell, Volume 41, Issue 4, 458-470, 18 February 2011
“TBK1 Directly Engages Akt/PKB Survival Signaling to Support Oncogenic Transformation”
Yi-Hung Ou, Michael Torres, Rosalyn Ram, Etienne Formstecher, Christina Roland, Tzuling Cheng,Rolf Brekken, Ryan Wurz, Andrew Tasker, Tony Polverino, Seng-Lai Tan, Michael A. White