Plasminogen activator inhibitor-1 (PAI-1) is a key regulator of cancer biology, influencing tumor progression, metastasis, and therapeutic resistance. Elevated levels of PAI-1 are consistently associated with poor prognosis across several malignancies, including breast, ovarian, lung, hepatobiliary, colorectal, and glioblastoma. Mechanistically, PAI-1 facilitates cancer cell survival, endothelial migration, and immune modulation. From a therapeutic standpoint, PAI-1 represents a promising target. Strategies to inhibit PAI-1, including small-molecule inhibitors and monoclonal antibodies, have demonstrated promise in preclinical research. Collectively, these findings underscore both the therapeutic potential and the translational challenges associated with targeting PAI-1 in future cancer treatment. This review examines the mechanistic foundations of the PAI-1 paradox, its prognostic and therapeutic implications in cancer, and the opportunities and challenges for clinical translation.
Shaer et al. (Wed,) studied this question.