Researchers identify pancreatic cancer protein drug target

A study has revealed the protein responsible for causing pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer.

The researchers, from the University of Texas MD Anderson Cancer Center, US, validated ubiquitin-specific protease 21 (UPS21) as a frequently amplified gene and a potential druggable target.

“The USP family is the largest group of enzymes known as cysteine proteases, which play an important role in tumour development and cancer stem cell biology,” said lead researcher Professor Ronald DePinho, MD. “Genomic analysis identified frequent amplification of USP21 in PDAC. This overexpression correlated with cancer progression in PDAC patient samples, drove malignant transformation of human pancreas cells and promoted mouse tumour growth.”

The team used USP21’s ability to deubiquitinate and stabilise TCF7, a transcription factor that promotes cancer cell stemness. By depleting USP21, pancreatic tumour growth was impaired.

This prompted the team to explore newly characterised genetic alterations in PDAC to identify and understand new oncogenes that may expand therapeutic strategies for the disease.

“USP21 knockout mice are normal, suggesting that targeting USP21 may represent a cancer-specific vulnerability,” said DePinho.

The findings were published in Genes & Development.