Neuropeptide Y in cancer-biological functions and potential clinical implications

Neuropeptide Y (NPY) is a sympathetic neurotransmitter widely distributed in the peripheral and central nervous system, affecting many physiological functions. Consequently, dysregulation of the NPY system contributes to numerous pathological disorders, including stress, obesity, and cancer. The pleiotropic functions of NPY in humans are mediated by G protein-coupled receptors (Y1R, Y2R, Y5R), which activate several signaling pathways and thereby regulate cell growth, differentiation, apoptosis, proliferation, angiogenesis, and metabolism. These activities of NPY are highly relevant to tumor biology and known hallmarks of cancer, including sustained proliferative potential, resisting cell death, angiogenesis, invasion, and metastases. In this comprehensive review, we describe the cellular functions of NPY and discuss its role in cancer pathobiology, as well as provide the current state of knowledge pertaining to NPY and its receptors in various cancer types. Moreover, we focus on potential clinical applications targeting the NPY system, such as its role as a prognostic and predictive factor, as well as its utility in cancer diagnostics, imaging, and treatment. Altogether, growing evidence supports the significant role of the NPY system in tumor pathobiology and implicates its potential therapeutic and diagnostic value in modern oncology.