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Plasminogen Activator Inhibitor-1 in Skin Malignancies: Therapeutic Implications of Its Inhibition
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Plasminogen Activator Inhibitor-1 in Skin Malignancies: Therapeutic Implications of Its Inhibition
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Journal Article
Plasminogen Activator Inhibitor-1 in Skin Malignancies: Therapeutic Implications of Its Inhibition
2025
Overview
Plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis, has emerged as a critical stromal factor that contributes to tumor progression in various malignancies, including skin cancers. Beyond its classical role in inhibiting plasminogen activators, PAI-1 exerts pleiotropic effects within the tumor microenvironment, promoting immunosuppression, angiogenesis, and extracellular matrix remodeling. This review highlights the tumor-promoting functions of PAI-1 in melanoma, cutaneous squamous cell carcinoma, cutaneous angiosarcoma and cutaneous T-cell lymphoma, with a particular focus on its modulation of tumor-associated macrophages, cancer-associated fibroblasts, and endothelial cells. We also discuss recent preclinical and clinical studies targeting PAI-1, including TM5614, a novel oral PAI-1 inhibitor currently under investigation in phase II /III trials. By summarizing the multifaceted roles of PAI-1 and its impact on the immune and stromal landscape of skin malignancies, this review provides a rationale for PAI-1 as a promising therapeutic target and calls for further clinical validation of PAI-1–directed therapies.
Publisher
MDPI AG
Subject
/ Animals
/ Carcinoma, Squamous Cell - drug therapy
/ Carcinoma, Squamous Cell - metabolism
/ Carcinoma, Squamous Cell - pathology
/ Cells
/ Humans
/ Ligands
/ Melanoma
/ Motility
/ PAI-1
/ Plasminogen Activator Inhibitor 1 - genetics
/ Plasminogen Activator Inhibitor 1 - metabolism
/ Plasminogen activator inhibitors
/ SASP
/ Skin
/ Skin Neoplasms - drug therapy
/ T cells
/ Tumor Microenvironment - drug effects
/ Tumors
