Cathepsin L as a Driver of Tumour Invasion and a Novel Therapeutic Target in Ovarian Cancer

Ovarian cancer is the most lethal gynaecological cancer, largely because it is often diagnosed late and shows strong tumour heterogeneity, therapy resistance, and rapid metastatic spread. A key driver of this aggressive behaviour is the tumour’s ability to reshape its surrounding microenvironment to support invasion, angiogenesis, and escape from treatment. Cathepsin L (CTSL), a lysosomal cysteine protease, has emerged as an important mediator of these processes and is gaining attention as both a prognostic marker and a potential therapeutic target. This review examines the diverse roles of CTSL in ovarian cancer progression, focusing on how its expression, localisation, and extracellular release are altered within the hypoxic and acidic conditions typical of the tumour microenvironment. It also outlines emerging therapeutic strategies aimed at targeting CTSL, including selective inhibitors, multi-cathepsin approaches, CTSL-activated prodrugs and antibody-drug conjugate linkers, and nanomedicine systems designed for tumour-specific delivery. Overall, the evidence highlights CTSL as a central regulator of invasion, angiogenesis, and relapse in ovarian cancer, underscoring its potential as a target for new therapies in aggressive disease.