From left: Dr. Frank Sicheri and Thanashan Rajakulendran, a PhD candidate, have shown how a type of protein called RAF acts as a signaling pathway that tells cells to grow.
September 10, 2009 - The Samuel Lunenfeld Research Institute's Dr. Frank Sicheri has co-authored a paper showing how protein molecules called RAF tell cells to grow, a discovery that could potentially lead to more effective chemotherapy drugs with fewer side effects.
The discovery is outlined in an article published in the scientific journal Nature, and co-authored by Dr. Sicheri and Dr. Marc Therrien of the Institute for Research in Immunology and Cancer at the Université de Montréal. The authors show that a type of protein called RAF - from a family of proteins known as kinase - function as a signaling pathway that tells cells to grow.
"When functioning normally, the pathway also signals that cells should eventually stop growing," says Thanashan Rajakulendran, a PhD candidate in Dr. Sicheri's lab who worked on the project. "But with cancer, RAF molecules act as a messenger that tells cells to keep growing indefinitely."
The researchers have discovered that RAF molecules must come into contact with one another in order to switch on the signaling pathway that causes cell growth. Currently, cancer drugs don't just target RAF molecules, but also affect other proteins from the kinase family. That can lead to the toxicity and side effects of chemotherapy.
The discovery could lead to potentially developing drugs that can bind to RAF molecules. This would lead to shutting down unchecked growth so that cancer cells die, as well as eliminating the unwanted side effects of current chemotherapy treatment.
"Protein kinases are the targets for some of the most successful anti-cancer drugs in the clinic," says Dr. Sicheri. "Now that we have discovered how to turn off the RAF protein without interfering with other proteins, we may be able to design drugs that have unprecedented precision in targeting cancer cells while reducing the toxic side effects for patients."