Chemical Inhibitor NGI-1 Curbs Lung Cancer

NGI-1 is a chemical inhibitor identified by researchers at the Yale School of Medicine which limits the growth of lung tumor cells. The inhibitor partially disrupts glycosylation and limits the spread of cancer cells.

Joseph Contessa, a senior author of the study describes, Glycosylation is an essential process for all cells, but researchers have long thought that there is no way to disrupt glycosylation in cancer cells without disrupting the same process in other cells and thereby causing serious harm. The inhibitor NGI-1, identified in the study affects tumor cells most severely. But the inhibitor does not harm other cells relatively.

“This is important to cancer research because what we’re looking for are therapies that don’t have a lot of effect on normal cells but do have a lot of effect on tumor cells, and this falls into that category,” stated Contessa. He serves as the director of Yale’s Central Nervous System Radiotherapy Program and an associate professor of therapeutic radiology and of pharmacology.

Researchers from the Broad Institute, the University of Massachusetts Medical School, the University of Kansas, the University of Georgia and the University of Texas Southwestern Medical Center were worked collectively for this study. To find a substance that could partially disrupt glycosylation, they screened over 350,000 chemical compounds. As a result of their efforts, they identified the inhibitor NGI-1. The first author of the study, Cecilia Lopez-Sambrooks stated that it was largely a team effort.

How The NGI-1 Inhibitor Works?

Oligosaccharyltransferase is an enzyme known as OST that transfers sugar molecules called oligosaccharides to receptor proteins. OST is used to glycosylate receptor proteins, which are required for the growth of tumor cells. NGI-1 blocks the glycosylation of OST and it leads to disruption of the cancerous cells growth.

According to Contessa, when the glycosylation of OST is blocked, the enzyme loses its ability to properly glycosylate the receptor proteins and it hinders the growth of tumor cells as a result. The study claims that NGI-1 only seems to block the spread of cells dependent on the protein receptors EGFR and FGFR. This indicates that the inhibitor NGI-1 can particularly target the growth of tumor cells while having a minimal effect on non-cancer cells.

Contessa likened the usage of NGI-1 to that of a “dimmer change.” He mentioned that, While most people have previously thought of glycosylation as something that can be switched on or off for all cells, NGI-1 only partially blocks glycosylation, which in turn has the most effect on tumor cells highly dependent on EGFR and FGFR.

Moving forward, Contessa said he hopes to bring the information from the study back to the clinic. He also mentioned that, ideally, this research can provide an alternative to other forms of treatment such as radiation therapy. Contessa recommended that since NGI-1 is a relatively small molecule, it’s likely that it could be ingested by the patient in the form of a pill.

“We have therapies, and they’re good therapies, but they’re not enough,” Contessa mentioned. “We need to take the next step.”