Proteolysis: new method developed to target cancer cells

A new method of activating specific molecules to target cancer cells while leaving healthy cells unharmed has been discovered by researchers at the University of Arizona Cancer Center. Published in the Journal of the American Chemical Society, Wei Wang, PhD, and his team developed click-release proteolysis, a new strategy to target chimeras, known as crPROTACs, which allows for the activation and release of PROTACs only in cancer cells.

“The studies open a new way to deliver anti-cancer drugs to cancer cells,” Wang said.

PROTACs are molecules that are designed by scientists  to break down specific proteins in the body and are currently being explored as a potential treatment for cancer.. However, they can pose harm to healthy cells because of uncontrolled protein breakdown.  

Wang’s research concentrates on the ubiquitin-proteasome pathway, an existing metabolic pathway in the human system that usually targets proteins for degradation and recycling. Premature drug activation and undesired side effects have been minimised by Wang utilising this pathway to specifically target cells at tumour sites.  The researchers found that the crPROTAC strategy successfully degraded proteins of interest in cancer cells. Wang’s approach derives from biorthogonal and click chemistry which was first developed by Carolyn Bertozzi, MS, PhD. She won the Nobel Prize in chemistry 2022 for this.

“Unlike many other drug delivery strategies, this approach will be very precise in targeting just the tumour,” Wang said. For this research and publication, he recently received the inaugural UArizona Cancer Center Research Award for Basic Science.