The GRPR signaling axis in cancer: Molecular mechanisms and oncogenic outcomes

The gastrin-releasing peptide (GRP) and its receptor (GRPR) constitute a biologically versatile signaling axis with essential physiological roles and growing relevance in cancer biology. GRPR is frequently expressed across multiple tumor types, where its activation modulates key cellular processes associated with malignant progression. Through engagement of diverse intracellular effectors and extensive crosstalk with receptor tyrosine kinases and other signaling systems, GRPR regulates pathways controlling tumor cell proliferation, survival, migration, invasion, angiogenesis, and transcriptional reprogramming. This review provides a comprehensive overview of the molecular mechanisms underlying GRPR-mediated signaling in cancer, integrating evidence from different tumor models. Importantly, the antitumor effects observed following pharmacological inhibition or genetic silencing of GRPR further underscore its therapeutic relevance. Collectively, these findings position GRPR as a central signaling integrator in tumor progression and a promising target for diagnostic, prognostic, and therapeutic strategies in oncology. • GRPR signaling plays context-dependent roles in cancer. • GRPR regulates proliferation, survival, inflammation, angiogenesis, and invasion. • Targeting GRPR reduces tumor growth and represents a promising therapeutic strategy.