The Role of LRP1 in Glioma Progression and Therapeutic Targeting: A Narrative Review

Gliomas are the most frequently encountered tumors in the central nervous system, with limited therapeutic effectiveness owing to their highly invasive nature, intratumoral heterogeneity, and presence of the blood–brain barrier (BBB). Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) is a large, multifunctional transmembrane endocytic receptor that regulates lipid metabolism, cell signaling, and endocytosis in various body tissues, including the brain. LRP1 mediates tumor cell proliferation, invasion, and angiogenesis in gliomas through various cellular signaling mechanisms, including the SP1/PI3K/AKT pathway and MAPK/ERK. The occurrence of LRP1 in the BBB and the recent identification of its increased expression in gliomas have suggested it as a promising therapeutic target for receptor-mediated nanoparticle delivery and treatment of gliomas. LRP1-mediated transcytosis is now being used to enhance the BBB penetration of chemotherapy drugs and radiosensitizers in gliomas, which has resulted in increased overall survival of patients secondary to increased antitumor effectiveness of therapies. Despite the effective preclinical role of LRP1-targeted therapy in glioma models, clinical translation is challenging due to significant heterogeneity in the expression patterns of LRP1 across various subtypes of gliomas, which may affect the clinical responsiveness of drug therapy. Furthermore, concerns related to the pharmacokinetics of therapy and receptor saturation kinetics have rendered its clinical applicability challenging.