University of Bath Scientists Discover Breakthrough Cancer Treatment Target
Scientists have identified promising drug candidates that permanently block a cancer-related protein, marking a significant advancement in targeting proteins previously considered difficult to treat with drugs.
Transcription factors are proteins that control gene activity and play a key role in cancer development. Efforts to develop small molecule drugs to inhibit them have largely been unsuccessful. In recent years, researchers have explored the use of peptides, which are small protein fragments, as potential inhibitors for these challenging targets.
A research team from the University of Bath has now detailed an approach to discovering peptides that selectively and permanently block a transcription factor known as cJun. This factor plays a role in cancer by binding to DNA and altering gene expression, contributing to uncontrolled cell growth.
The new drug discovery platform is called the Transcription Block Survival (TBS) assay. This technology screens a large number of peptides to identify those capable of switching off transcription factors linked to cancer. Previous work had identified reversible inhibitors of cJun, but this latest research has succeeded in finding peptides that bind irreversibly within cells.
cJun functions as a pair, with two identical halves binding to DNA. The researchers developed a peptide inhibitor that attaches to one half of cJun, preventing it from forming pairs and stopping its interaction with DNA. By modifying this peptide, they achieved irreversible binding, ensuring that the transcription factor remains permanently blocked.
The TBS assay was designed by inserting binding sites for cJun into an essential gene in lab-grown cells. When cJun binds to the gene, it disrupts its function, leading to cell death. However, if cJun is inhibited by the peptide, the gene remains active, allowing the cell to survive. This screening method ensures that only effective peptide inhibitors with the ability to enter cells and remain active are selected.
