The Proteolytic Landscape of Ovarian Cancer: Applications in Nanomedicine

Abstract

Ovarian cancer (OvCa) is one of the leading causes of mortality globally with an overall 5-year survival of 47%. The predominant subtype of OvCa is epithelial carcinoma, which can be highly aggressive. This review launches with a summary of the clinical features of OvCa, including staging and current techniques for diagnosis and therapy. Further, the important role of proteases in OvCa progression and dissemination is described. Proteases contribute to tumor angiogenesis, remodeling of extracellular matrix, migration and invasion, major processes in OvCa pathology. Multiple proteases, such as metalloproteinases, trypsin, cathepsin and others, are overexpressed in the tumor tissue. Presence of these catabolic enzymes in OvCa tissue can be exploited for improving early diagnosis and therapeutic options in advanced cases. Nanomedicine, being on the interface of molecular and cellular scales, can be designed to be activated by proteases in the OvCa microenvironment. Various types of protease-enabled nanomedicines are described and the studies that focus on their diagnostic, therapeutic and theranostic potential are reviewed.

Keywords: cathepsin; kallikrein; matrix metalloproteinase; nanomedicine; nanoparticle; ovarian cancer; protease; trypsin; urokinase plasminogen activator.

Figure 1

Schematic of Tumor Protease Cascade in OvCa. Red/flat line represents inhibition and decreased tumorigenic activty and green/arrow represents cleavage or activation increasing tumorigenic activity. Dashed line represents IGFBP binding of IGF and leading to decreased circulation of IGF.

Figure 2

Schematics of NP structures used in OvCa detection and treatment. Created with BioRender.com.