Congratulations to Dr Milon Mondal and Dr Dan Conole on their review article!

Breast cancer has the highest incidence and death rate among cancers in women worldwide. In particular, metastatic Estrogen Receptor negative (ER–) breast cancer and Triple-Negative Breast Cancer (TNBC) subtypes have very limited treatment options, with low survival rates.

Ubiquitin carboxyl terminal hydrolase L1 (UCHL1), a ubiquitin C-terminal hydrolase belonging to the deubiquitinase (DUB) family of enzymes, is highly expressed in these cancer types, and several key reports have revealed emerging and important roles for UCHL1 in breast cancer. However, selective and potent small molecule UCHL1 inhibitors have been disclosed only very recently, alongside chemical biology approaches to detect regulated UHCL1 activity in cancer cells.

In this review, Dr Mondal, Dr Conole, and Dr Jaya Nautiyal (Faculty of Medicine) discuss the tools that will enable novel insights into oncogenic mechanisms driven by UCHL1. They also carry out identification of substrate proteins deubiquitinated by UCHL1, with the ultimate goal of realizing the potential of UCHL1 as a drug target in breast cancer.