LAUSR

ABSTRACT Introduction In view of other candidate proteins from the cathepsin family of proteases holding great potential in being targeted during cancer therapy, the importance of Cathepsin B (CtsB) stands out as being truly exceptional. Based on its contribution to oncogenesis, its intimate connection with regulating apoptosis and modulating extracellular and intracellular functions through its secretion or compartmentalized subcellular localization, collectively highlight its complex molecular involvement with a myriad of normal and pathological regulatory processes. Despite its complex functional nature, CtsB is emerging as one of the few cathepsin proteases that has been extensively researched to yield tangible outcomes for cancer therapy. Areas covered In this article, we review the scientific literature that has justified or shaped the importance of CtsB expression in cancer progression, from the perspective of highlighting a paradigm that is rapidly changing from basic research toward a broader clinical and translational context. Expert opinion In doing so, we detail its maturation as a diagnostic marker through describing the development of CtsB-specific Activity-Based Probes, the rapid evolution of these toward a new generation of Prodrugs, and the evaluation of these in model systems for their therapeutic potential as anti-cancer agents in the clinic.