Human cells are constantly developing, dividing, and dying. In a healthy individual, these processes are kept in balance; proto-oncogenes promote cell growth, while anti-oncogenes suppress it. Mutations in either type of gene can lead to cancerous cell growth.
NYU Abu Dhabi Postdoctoral Associate Louise Ashall, a cell biologist, has been working within a team from NYUAD's Dore Laboratory to develop ways of inhibiting a group of oncogenes called Ras proteins, "the most commonly mutated oncogenes, accounting for 20 percent to 30 percent of all human cancers," Ashall said.
Enzymes called CaaX proteases play an essential role in Ras maturation. So medicinal chemists at the Dore Lab synthesized molecules that inhibit one of the CaaX enzymes that Ras proteins need to function. "These inhibitors are small molecules that interfere and block the function of the CaaX protease enzyme, thus stopping the protease from performing its role," Ashall explained. "Our aim is to inhibit Ras indirectly through reducing the activity of the CaaX protease enzyme."
Ashall has been testing the CaaX inhibitors in a live cell assay using a human colon cancer cell line. Using fluorescent "reporter" genes, she can measure the effectiveness of CaaX inhibitors to disrupt Ras from the cell membrane and consequently stop pathways that promote cell growth.
Ashall is "interested in how cell signaling pathways are controlled and may become deregulated, which can lead to diseases" such as cancer.
Ashall hopes the team's research into CaaX inhibitors will lead to advances in "gaining a better understanding of the mechanisms that are involved" in signaling cell growth. This "will allow scientists to manipulate signaling pathways to potentially design better drugs for control and treatment of diseases," she said.