Matrix Metalloproteinase-9: A Key Diagnostic Biomarker in Cancer Progression

Matrix metalloproteinase-9, also known as MMP-9, gelatinase B, or 92 kDa type IV collagenase, is an enzyme that belongs to the matrix metalloproteinase (MMP) family. It is involved in the remodeling of the extracellular matrix in various physiological and pathological processes. MMPs are expressed in low, tightly regulated concentrations; their overexpression or dysregulation can lead to diseases, including cancer. MMP-9 is increasingly recognized as a significant drug target in cancer therapy due to its involvement in tumorigenesis, including processes like cell migration, angiogenesis, and pro-apoptotic and anti-apoptotic activities. Despite MMP-9's significance as a cancer target, developing effective inhibitors remains challenging due to MMP structural similarities. Utilizing MMP-9 as a cancer biomarker could advance cancer diagnosis, prognosis, disease monitoring, recurrence prediction, and other procedures. Biosensors are emerging as pivotal tools in cancer diagnosis and treatment, leveraging their ability to detect specific biomarkers associated with various cancers. Recent advancements have led to the development of both cleavage-based and non-cleavage-based biosensors that enable rapid and sensitive analysis at clinically relevant concentrations of biomarkers while allowing specificity and low detection limits, enhancing point-of-care diagnostics. The cleavage-based biosensors leverage the enzymatic activity of MMP-9, utilizing substrates that are specifically cleaved by MMP-9, while the non-cleavage- based biosensors employ affinity methods, such as antibodies and aptamers for detection. The present review aims to evaluate the role of MMP-9 as a significant biomarker in cancer and its detection through innovative biosensor technologies, while exploring its involvement in various cancer- related processes. This review discusses the significance of MMP-9 in cancer progression, highlighting clinical trials that assess MMP-9 inhibitors as potential therapeutic agents to halt metastatic spread. Furthermore, MMP-9 is detected via biosensors, and insights into the translational potential of MMP-9 both as a biomarker for early cancer detection and a viable target for therapeutic intervention are provided, ultimately contributing to improved patient outcomes in oncology.