Progress in the pathogenesis and treatment of pituitary neuroendocrine tumors (PitNETs): From molecular mechanisms to emerging therapies

Pituitary neuroendocrine tumors (PitNETs), arising from anterior pituitary neuroendocrine cells, constitute 10–15 % of intracranial tumors. Though mostly benign, their location near critical structures like the optic chiasm and cavernous sinus causes severe neuroendocrine dysfunctions and mass effects. The 2022 WHO classification rebranded them from "pituitary adenomas" to emphasize their neuroendocrine lineage, yet challenges in prognostic prediction retain traditional terminology. Pathogenesis involves genetic mutations GNAS in GH-PitNETs, USP8 in ACTH-PitNETs), epigenetic dysregulation (METTL3-mediated m6A methylation), and signaling pathway aberrations (cAMP-PKA activation). Current treatments—surgery, dopamine agonists, somatostatin analogs, and radiation—face limitations like recurrence and side effects. Emerging strategies include targeted therapies (BET inhibitors) and immune checkpoint blockade, but tumor heterogeneity and lack of predictive biomarkers remain key obstacles. This review synthesizes pathogenesis, therapeutic advances, and research gaps to foster precision medicine and novel diagnostic/treatment paradigms for PitNETs.