The role of ERK signaling pathway in pituitary adenomas: from molecular mechanisms to targeted therapy

ERK, a core member of the MAPK family, operates through the classical Ras/Raf/MEK/ERK signaling cascade. Abnormal activation of this pathway is closely associated with malignant tumor progression and represents a critical target in anticancer drug development. In this article, we systematically describe the regulatory network of the ERK pathway, including negative feedback mechanisms, cross-pathway interactions, non-coding RNAs, and epigenetic regulation, with a particular focus on ERK's dual role-promoting both cell proliferation and apoptosis-in pituitary adenomas compared to other tumors. Additionally, we explore emerging ERK-targeted therapies and their associated resistance mechanisms. Despite substantial research on ERK, further investigation into its underlying mechanisms is warranted. We propose the construction of computational modeling approaches to analyze these complex regulatory relationships and to develop precise combination therapies aimed at overcoming resistance. Such strategies could enable personalized treatment and offer more effective solutions for managing pituitary tumors and other malignancies.